discrete PEGs - Peptides International

Transcription

many needs, one solution:
O
(
®
PEG
PEG
PEG
P
P
P
O
®
)x
O
O
O
®
X = 4, 8, 12, and 24 Single Compound
®
MW ~ 200 - 1000 • 20 Å - 90 Å
ethylene oxide
non-immunogenic
10180
®
monodisperse PEG
P
P
spacer
S
reproducible
reproducible
reproducible
PEG
PEG
cross-linker
O
water soluble
high purity
consistent
discretePEG
hydrophilic
organic sol u bl e
OH
A Quanta Leap: discrete PEGs
Peptides International is pleased to introduce monodisperse, discrete PEG derivatives (dPEG®) to our colleagues
around the world. Through a distribution agreement with Quanta BioDesign, dPEG® reagents will complement the
synthetic portfolio of PI offerings. PI and Quanta anticipate continued development of new materials for applications
in peptide chemistry. Please contact us for further information or to discuss a new project idea.
Polyethylene glycol (PEG) is a polymer made from condensation of ethylene oxide and has been used in
a wide variety of well-known consumer products. PEG’s hydrophilic and weak immunogenic properties
make it ideal for drug delivery and new therapies. The attachment of PEG linkers to therapeutic proteins
can confer these properties upon the modified protein, increasing stability and half-life in vivo. However,
PEG polydispersity and the resulting highly heterogeneous mixtures, adversely affect cost and production
aspects of drug development. Attempts to synthesize monodisperse PEG have been limited by long reaction
times, low yields and unwanted by-products.
Quanta BioDesign has developed efficient and rapid methods for chemical synthesis of monodisperse,
discrete PEG, or dPEG™, of any specific MW. The dPEG®’s are not purified from a polymeric mixture
and hence contain no other PEG homologues (only the one selected as the desired product), resulting in a
single compound with a single molecular weight. Using dPEG®s should significantly decrease cost and
time associated with synthesis by reducing problems associated with using conventional PEGs. Peptides
International is now offering dPEG® derivatives, carefully selected for your protein labeling and peptide
synthetic needs. For an expanded listing of dPEG™ related products from Peptides International, please visit
http://pepnet.com/dPEG.pdf.
US Patent 20060020134
Research Today. Cures Tomorrow. We'll Be There.
About Us
A Louisville,Kentucky
Presence...
In 2006, we completed a new facility expansion that allows us to increase our product portfolio and expand
our custom services.
• Additional labs for custom synthesis and special
projects
• Scale-up space
• Dedicated QC and analytical testing labs
• Additional product / inventory storage
• Expanded order processing and customer service
areas
...With International Reach
And with a customer base that truly spans
the globe, Peptides International lives up
to its name daily. We ship our products
to laboratories from Ann Arbor to Zurich,
supporting research in over 40 countries.
Respected institutions, universities, research
facilities, and companies every-where have
come to rely on Peptides International as their
supplier of choice.
A Quanta Leap: discrete PEGs
PEG
®
P
Peptides International is pleased
to offer monodisperse, discrete
PEG derivatives (dPEG®) to
our colleagues around the world.
Through a distribution agreement with Quanta BioDesign,
dPEG® reagents complements the synthetic portfolio of PI
offerings. PI and Quanta anticipate continued development
of new materials for applications in peptide chemistry. Please
contact us for further information or to discuss a new project
idea.
Polyethylene glycol (PEG) is a polymer made from
condensation of ethylene oxide and has been used in a
wide variety of well-known consumer products. PEG’s
hydrophilic and weak immunogenic properties make it
ideal for drug delivery and new therapies. The attachment
of PEG linkers to therapeutic proteins can confer these
properties upon the modified protein, increasing stability
and half-life in vivo. However, PEG polydispersity and
the resulting highly heterogeneous mixtures, adversely
affect cost and production aspects of drug development.
Attempts to synthesize monodisperse PEG have been
limited by long reaction times, low yields and unwanted
by-products.
8
Quanta BioDesign has developed efficient and rapid
methods for chemical synthesis of monodisperse, discrete
PEG, or dPEG®, of any specific MW. The dPEG®’s are not
purified from a polymeric mixture and hence contain
no other PEG homologues (only the one selected as
the desired product), resulting in a single compound
with a single molecular weight. Using dPEG®s should
significantly decrease cost and time associated with
synthesis by reducing problems associated with using
conventional PEGs. Peptides International is now offering
dPEG® derivatives, carefully selected for your protein
labeling and peptide synthetic needs.
About Quanta BioDesign:
Founded by Dr. Paul D. Davis in 1999,
Quanta Biodesign is committed to the
development of a full range of discrete
polyethylene glycol (dPEG®) pegylation
reagents. Quanta’s dPEG® currently have
MW’s from 200 D to over 2400 D, with broad
applications in diagnostics, therapeutics,
peptide synthesis, oligonucleotide synthesis,
and nanotechnology.
Order Hotline 1-800-777-4779 502-266-8787
dPEG® (discrete polyethylene glycol) Product Supplement
Peptides International specializes in a wide variety of
high purity, biologically active peptides and peptiderelated products and services. Peptides International
manufactures and distributes biochemical products for
major research institutions throughout the world. Our
research and manufacturing facility is located in the
Bluegrass Industrial Park in Louisville and is involved
in peptide synthesis, new product development,
custom contract synthesis, combinatorial libraries, quality control operations, and a variety of research interests. Our proprietary
research interests include new applications
for CLEAR resins, MMP inhibitors, combinatorial chemistry, unusual amino acid synthesis, including asymmetric synthesis and
amide bond surrogates, and peptide mimetics.
The company was awarded the first NSF SBIR
grant funded in the state of Kentucky
and is the current recipient of a SBIR
Phase I grant titled, “Novel Peptide Libraries for Early Cancer Detection”.
PEPTIDES INTERNATIONAL
Since 1983, Peptides International
has been known for its relentless
commitment to quality, service, and
integrity. In a time when the company
you bought from yesterday is gone
today, you can be assured of the
longevity of Peptides International. That longevity, a
consequence of an enviable reputation, stands as an
enduring testement to the standards held by founder Dr.
Arno Spatola since the very beginning, and continue to
this day.
PRODUCT
CodeQty
dPEG® Biotinylation Reagents
•
•
•
Very water soluble, hydrophilic and eliminates non-specific binding.
Non-antigenic and non-immunogenic spacer arm
The dPEG® pegylation spacer and its properties eliminates aggregation and precipitation when labeling antibodies and other biological materials, and will
also significantly increase S/N in analytical applications as well.
Protocol for in situ activation to the NHS ester:
Use a 10-20% molar excess of EDC and NHS in dry methylene chloride (dried over 3A molecular sieves). Add a methylene chloride solution of the acid to the dry
reagents under dry conditions. Stir for several hours or overnight, then evaporate the solvent and use. Can also treat reaction mixture with a small amount of
silica gel to adsorb the excess EDC and the urea by-product, filter, then evaporate the solvent and use. Note of caution: The NHS should be added with the EDC to prevent formation of the anhydride. Also, can be used for
peptide labeling using a variety of activating “concoctions,” which can also be used for direct coupling to other amines.
Reference:
Greg T. Hermanson, Bioconjugate Techniques, 2nd Ed, Academic Press, Inc., San Diego, CA, (2008).
Protocol:
See Hermanson pg. 728 for a typical protocol for a antibody or protein biotinylation using an in situ activated form of DPG-5706-PI. Generally customers use this
when they have their favorite way of activating the acid, as opposed to using our dPEG®12 pegylation spacer containing biotin reagent. The reagent can be pre-
dissolved in an organic solvent or can be directly dissolved in your reaction medium based on its inherent water solubility. Also, see above in situ activation
procedure.
NHS-dPEG®4 Biotin
DPG-5701-PI
50 mg
4 °C Chain length from amide to terminal carbonyl is 19.2 Angstroms and 16 atoms spacer
1g
O
Ideal spacer length for binding streptavidin conjugates
O
H
O
O
N
(M.W. 588.67)
O
N
O
HN
®
N
O
O
O
Amine reactive biotinylation reagent with a dPEG pegylation spacer arm; activate in situ
O
H
S
• The dPEG® pegylation spacer and its properties eliminate aggregation and precipitation when labeling antibodies
10200 and other biological materials, and will also significantly increase S/N in analytical applications as well.
silica gel to adsorb the excess EDC and the urea by-product, filter, then evaporate the solvent and use.
Note of caution: The NHS should be added with the EDC to prevent formation of the anhydride. Also, can be used for peptide labeling using a variety of activating
“concoctions,” which can also be used for direct coupling to other amines.
Protocol:
See Hermanson, pg. 728 for a typical protocol for a antibody or protein biotinylation using an in situ activated form of DPG-5706-PI. The reagent can be pre dissolved in an organic solvent or can be directly dissolved in a reaction medium based on its inherent water solubility.
NHS-dPEG®12 Biotin
DPG-5703-PI
25 mg
4 °C 47.6 Angstrom and 40 atoms spacer
500 mg
(M.W. 941.09)
1g
Amine reactive biotinylation reagent with a dPEG® pegylation spacer arm; activate in situ
O
H
N
H
N
N
H
S
10198
Order Hotline 1-800-777-4779 502-266-8787
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
N
O
PRODUCT
CodeQty
NHS-dPEG®4 Biotinidase-Resistant Biotin
DPG-5702-PI
50 mg
4 °C Amine reactive biotinylation pegylation reagent with a dPEG®4 spacer
500 mg
1g
(M.W. 673.78)
H
O
O
O
N
H
Amine Reactive Biotinylation Reagent
O
O
O
N
•
•
•
•
•
HN
N
H
S
N
O
O
O
O
O
Amine reactive biotinylation pegylation reagent with a dPEG® spacer, the perfect length for most applications.
10202
Biotindase resistant - vital especially for in vivo work or clinical analysis.
This reagent gives the spacer length with the pegylation arm for optimal biotin binding with streptavidin conjugates; chain length from amide to terminal carbonyl is 19.2 Angstroms. Designed to be the same length as the LC-LC spacer, which is ideal for the streptavidin binding pocket.
Eliminates non-specific binding issues, things like aggregation and precipitation when labeling antibodies and other biological materials (a problem with conventional biotinylation reagents).
Protocol:
The pegylation reagent can be pre-dissolved in an organic solvent OR can be directly dissolved in pure water, but must be used immediately. The reaction is best run between pH 7.2 and 8 using a non-amine buffer, e.g., PBS pH 7.2. Typical incubation times will be about 2 hours on ice and 30 minutes at RT. For large molecules the unreacted biotinylation reagent can be removed with gel filtration or dialysis.
D. Scott Wilbur, et al., Bioconjugate Chemistry, 17(6), 1514-1522 (2006).
Fmoc-Amido-(dPEG®4 Biotin) Acid
DPG-5704-PI
50 mg
4 °C Spacer properties: 18.1 Angstrom and 17 atoms spacer
100 mg
(M.W. 827.98)
1g
Biotinylation reagent in peptide synthesis, with built-in
S
O
pegylation spacer arm for optimal Streptavidin binding
O
O
N
H
O
O
N
H
NH
HN
O
O
O
N
10602
O
•
•
•
•
OH
NEW biotinylation reagent in peptide synthesis, with built-in pegylation spacer arm for optimal Streptavidin binding.
An N-Fmoc protected hydrophilic, non-immunogenic biotinylation pegylation reagent for peptide synthesis.
Useful for incorporating our powerful dPEG®4-biotin directly into the peptide synthesis, without having to label a side chain or label the N-terminus.
Incorporation of the dPEG®4 spacer with the biotin will increase water solubility and reduce or eliminate aggregation, while having the length in the spacer to
optimize the interaction with the avidin conjugate of your choice.
Order Hotline 1-800-777-4779 502-266-8787
O
PRODUCT
CodeQty
dPEG® Biotin Acid
•
•
•
•
•
•
Imparted physical properties are the biotin same as the dPEG®X NHS esters (DPG-5701-PI, DPG-5703-PI); the labeled compound becomes very hydrophilic because of
the dPEG® pegylation spacer, making the biotin very available for streptavidin binding in the capture/binding step.
The DPG-5705-PI pegylation spacer is the same length as DPG-5701-PI and DPG-5703-PI, respectively, and its length is optimal for rapid and tight avidin/SA binding
properties.
Very water soluble, hydrophilic and eliminates non-specific binding.
DPG-5703-PI has a longer 47.6 Angstrom spacer: the longer pegylation arm gives ready accessibility to the biotin by the streptavidin/avidin conjugate binding; also where
the amine of the biotinylation site may be buried, the longer arm is ideal for giving accessibility to the binding conjugates.
Non-antigenic and non-immunogenic spacer arm.
The dPEG® pegylation spacer and its properties eliminates aggregation and precipitation when labeling antibodies and other biological materials, and will also
significantly increase S/N in analytical applications as well.
silica gel to adsorb the excess EDC and the urea by-product, filter, then evaporate the solvent and use.
Note of caution: The NHS should be added with the EDC to prevent formation of the anhydride. Also, can be used for peptide labeling using a variety of activating
“concoctions,” which can also be used for direct coupling to other amines.
Reference:
Protocol:
See Hermanson, pg. 728 for a typical protocol for a antibody or protein biotinylation using an in situ activated form of DPG-5706-PI. Generally customers use this when
they have their favorite way of activating the acid, as opposed to using our dPEG®12 pegylation spacer containing biotin reagent. The reagent can be pre-dissolved in
an organic solvent or can be directly dissolved in your reaction medium based on its inherent water solubility. Also, see above in situ activation procedure.
dPEG®4 Biotin Acid
DPG-5705-PI
50 mg
4 °C Chain length from amide to terminal carbonyl is 19.2 Angstroms and 16 atoms spacer
1g
(M.W. 491.60)
O
H
N
O
HN
O
O
N
H
S
O
O
O
OH
10199
dPEG®12 Biotin Acid
DPG-5706-PI
50 mg
1g
(M.W. 844.02)
Amine Reactive Biotinylation Reagent; Activate in situ
O
O
NH
NH
S
O
N
H
O
O
O
O
O
O
O
O
O
O
O
O
OH
10197
NHS-Biotin
DPG-5707-PI
100 mg
4 °C (M.W. 341.38)
1g
Amine Reactive Label with Aliphatic Spacer
O
NH
HN
O
S
O
O N
O
10205
• Utilizes Quanta’s exclusive synthetic process.
• Efficient label for certain peptides and nucleic acids.
• Permeates cell membranes.
Protocol:
Hermanson, pg. 512, except make a 40 mg/ml solution of the NHS-biotin in dry DMF. The use of dry DMF is critical. This can easily be obtained by placing 3 Angstrom
or 4 Angstrom molecular sieves into reagent grade DMF, shaking and letting stand at least overnight. If possible, handle the NHS-biotin under an inert atmosphere. It
has been found that handling these materials in an Atmosbag, available from Sigma-Aldrich, under argon (preferred) or nitrogen, is the best, most convenient, and inex- pensive means of handling these moisture sensitive materials. The remaining solid NHS-biotin should be stored under an inert gas (argon preferred) at about 4°C.
Order Hotline 1-800-777-4779 502-266-8787
PRODUCT
CodeQty
NHS-LC-Biotin
DPG-5708-PI
50 mg
4 °C 8.8 Angstrom spacer
1g
(M.W. 454.54)
Amine Reactive Label with Extended Aliphatic Spacer
O
O
NH
HN
O
O
N
H
S
O
N
O
10206
• Contains extended spacer arm to enhance binding with streptavidin.
• Requires use of DMF, but is more soluble than NHS-biotin.
• 8.8 Angstrom hydrophilic spacer arm (non-dPEG®).
Carbonyl / Carboxyl Reactive Reagents
•
•
•
•
A carboxy protected dPEG®x amino acid pegylation reagent
dPEG® pegylation spacer and modifier with a reactive amine and a t-butyl protected carboxylic acid.
dPEG® pegylation spacer is extremely hydrophilic, will enhance the water solubility of a compound in which it is incorporated and reduce non-specific binding where
applicable. The spacer is also non-immunogenic. The ester is both water soluble, as well as in common used organic solvents of moderate prolarity.
t-Butyl group:
– Is easily removed with TFA (25% TFA in CH2Cl2, ice bath/0° C, takes about 5 h).
– Provides a potentially powerful purification handle due to its hydrophobicity. Subsequently it is removed to perform additional chemistry. This applies best when using
normal phase (e.g., silica gel) chromatography.
– Neutralizes the zwitterion of the amino acid for better reactivity at the amine.
– Reacts with carboxylic acids and other carbonyls.
Note: Carbodiimides other than EDC can be used, but the water soluble and polar nature of the by-products makes work-up very efficient with EDC. DCC is also very
good, if one is able to remove all of the DCU. These reactions are best carried out at –10 - 0°C. The reactions all need to be monitored by chromatography, TLC, or
HPLC.
Protocols:
The following are general use guidelines for reaction with:
a.Reaction with an active ester: Find a solvent in which active ester is soluble (methylene chloride is a preferred solvent) and dissolve the ester in the dry solvent,
add triethylamine, then add the amine, either neat or drop wise as a solution in the reaction solvent. Use at least a 10% excess of all reagents relative to the
active ester. This can be carried out at ambient temperatures.
b.Reaction with a free acid: generate the active ester in situ with EDC and NHS or HOBt, then add the triethylamine, followed by the amino-dPEG4 t-butyl ester;
or ii) combine the acid, NHS or HOBt, TEA, and the amino-dPEG®4 t-butyl ester, and add a solution of the EDC. Use at least a 10% excess of reagents relative
to the acid.
Amino-dPEG®2 t-Butyl Ester
DPG-5709-PI
100 mg
4 °C 10.9 Angstroms and 10 atoms spacer (nitrogen to carbonyl carbon)
500 mg
(M.W. 233.30)
1g
Carboxy-Protected dPEG®2 Amino Acid
O
H2N
O
O
O
10264
DPG-5711-PI
100 mg
500 mg
(M.W. 321.41)
1g
O
O
H2N
O
O
O
O
10221
Order Hotline 1-800-777-4779 502-266-8787
PRODUCT
CodeQty
Amino-dPEG®4 Methyl Ester Kit
DPG-5712-PI
100 mg
500 mg
(M.W. 279.33)
1g
Methyl protected dPEG® amino acid: dPEG® pegylation spacer and modifier containing a reactive amine
O
H2N
O
O
O
O
OCH3
Note: The amino-dPEG® methyl esters are not stable upon prolonged storage. There are kits developed in order to make these valuable pegylation compounds
available in a pure form in situ.
10330
Each kit contains three component parts: a) 1 eq. of amino-dPEG® acid;
b) 1.5 eq. of p-toluene sulfonic acid;
c) sufficient dry methanol for the package size.
• Methyl protected dPEG® amino acid: dPEG® pegylation spacer and modifier containing a reactive amine.
• Methyl group is removed with mild base once the amine is reacted.
• dPEG® pegylation spacer is hydrophilic, highly water soluble and non-immunogenic. The ester is water soluble, as well as being soluble in a variety of organic solvents
especially methylene chloride.
• Contrasting the t-butyl group, the methyl group can be easily removed with base, either KOH or with a carbonate base, e.g., potassium carbonate in aqueous methanol.
This can be done in an aqueous or combination aqueous organic solvent system. The specific conditions are going to be dictated by the stability of the system into
which the methyl ester is being introduced.
• Methyl group can also, like the t-Butyl group provide a potential purification handle due to its hydrophobicity. Subsequently it is removed to perform additional chemistry.
This applies best when using normal phase (e.g., silica gel) chromatography. The methyl group neutralizes the zwitterion of the amino acid for better reactivity at the
amine
Protocol :
a) Preparation of the methyl ester in situ: In a dry flask, add the 100 mg of p-toluenesulfonic acid and place in an ice bath. While keeping the contents under a
dry atmosphere (e.g. with a drying tube or with nitrogen) slowly add 1 ml of dry methanol with stirring, and then stir for 5 minutes at this temperature.
Subsequently, add the 100 mg of the amino-dPEG® acid in one portion to this solution and allow the mixture to stir at ambient temperature until the reaction is
complete by TLC.1 This will typically take about 3-4 hours. To use the amino-dPEG®4 methyl ester, you can proceed with the methanol solution, if this solvent is
compatible, or remove the solvent and replace it with one that is, the choice can include water. At this stage the product is stable if stored at +4° C or lower
for short periods of time (days). When using the product, you will need to compensate for the 1.5 equivalents of p-toluenesulfonic acid in the product with the
supplemental addition of 1.5 equiv. of base. When reacting in an organic solvent we most often use triethylamine, diisopropylethylamine or 2,6-lutidine, e.g., when
reacting with active esters. IN AQUEOUS, care must be taken NOT to hydrolyze the methyl ester at elevated pHs (>7).
1. TLC data: The solvent is typically something like methanol: methylene chloride: ethyl acetate: ammonium hydroxide, 1:2:2:0.2 or 1 ml: 2 ml: 2 ml: 10 drops,
run on a silica gel normal phase plate and developed with a ninhydrin spray (e.g. the Rf of the amino-dPEG®4 methyl ester is about 0.4). When the reaction is
complete, it will be one clean spot on the plate.
2. Important Note: Although the amino-dPEG® methyl esters were previously available as an individual products, it has been found that upon extended storage
the material polymerizes (amine reaction with the methyl ester).
b) Reaction with active ester: Find a solvent in which active ester is soluble (methylene chloride is a preferred solvent) and dissolve the ester in the dry solvent,
add triethylamine, then add the amine, either neat or drop wise as a solution in the reaction solvent. Use at least a 10% excess of all reagents relative to the
active ester. This can be carried out at ambient temperatures.
c) A free acid: Generate the active ester in situ with EDC and NHS or HOBt, then add the triethylamine, followed by the amino-dPEG®4 t-butyl ester; or ii)
combine the acid, NHS or HOBt, TEA, and the amino-dPEG® methyl ester, and add a solution of the EDC. Use at least a 10% excess of reagents relative
to the acid. Note: Carbodiimides other than EDC can be used, but the water soluble and polar nature of the by-products makes work-up very efficient with EDC.
chromatography, TLC, or HPLC. DCC is also very good, if one is able to remove all of the DCU. These reactions are best carried out at –10 - 0° C. The
reactions all need to be monitored by TLC or NPLC.
Order Hotline 1-800-777-4779 502-266-8787
1
PRODUCT
CodeQty
Amino-dPEG® Acids
Soluble and non-immunogenic.
Zwitterionic, extremely water soluble, and soluble in methylene chloride.
Unprotected amino acid for those who prefer the potential simplicity of not having to remove one more protecting group. Pegylation reagent reacts selectively as the
amine with NHS and other active esters in the presence of a 3º amine, e.g., TEA.
The dPEG® amino acids can also be used in situ to make the methyl ester, which is generally not stable for extended periods of storage (see DPG-5712-PI for kit and
protocol).
Spacer will minimize or eliminate aggregation problems with its incorporation into peptides and related compounds.
•
•
•
•
•
Application:
Surface and particle modification with terminal carboxyl functionality.
• GREAT for coating beads in order to reduce non-specific binding problems.
• Reacts like common amino acids. The amine can be reacted selectively in the presence of an appropriate base with an activated ester.
• Can be reacted in solvents as non-polar as methylene chloride.
Amino-dPEG®4 Acid
DPG-5710-PI
100 mg
500 mg
(M.W. 265.30)
1g
Unprotected amino acid for those who prefer the potential simplicity of not having
to remove one more protecting group. Pegylation reagent reacts selectively
as the amine with NHS and other active esters in the presence of a 3o amine, e.g., TEA. O
O
H2N
O
O
O
OH
Amino-dPEG®8 Acid
DPG-5713-PI
100 mg
H2N
O
O
O
O
O
O
O
O
OH
O
1g
(M.W. 441.51)
10244
Unprotected dPEG®8 Amino Acid
Amino-dPEG®12 Acid
DPG-5715-PI
100 mg
10277
4 °C 46.5 Angstroms and 40 atoms spacer 1g
(M.W. 617.72)
Unprotected dPEG®12 Amino Acid
HO
H2N
O
O
O
O
O
O
O
O
O
O
O
O
O
10287
Amino-dPEG®24 Acid
DPG-5717-PI
100 mg
4 °C 89 Angstroms and 76 atoms spacer 1g
(M.W. 1146.35)
Unprotected amino acid for those who prefer the potential simplicity of not having
to remove one more protecting group. Pegylation reagent reacts selectively as the
amine with NHS and other active esters in the presence of a 3° amine, e.g., TEA.
H2N
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
OH
O
O
10317
2
Order Hotline 1-800-777-4779 502-266-8787
PRODUCT
CodeQty
Amino-dPEG® t-Butyl Esters
•
•
•
•
A carboxy protected dPEG®x amino acid pegylation reagent.
dPEG® pegylation spacer and modifier with a reactive amine and a t-butyl protected carboxylic acid.
dPEG® pegylation spacer is extremely hydrophilic, will enhance the water solubility of a compound in which it is incorporated and reduce non-specific binding where
applicable. The spacer is also non-immunogenic. The ester is both water soluble, as well as in common used organic solvents of moderate prolarity.
t-Butyl group:
– Is easily removed with TFA (25% TFA in CH2Cl2, ice bath/0° C, takes about 5 h).
– Provides a potentially powerful purification handle due to its hydrophobicity. Subsequently it is removed to perform additional chemistry. This applies best when using
normal phase (e.g., silica gel) chromatography.
– Neutralizes the zwitterion of the amino acid for better reactivity at the amine.
– Reacts with carboxylic acids and other carbonyls.
Protocols:
The following are general use guidelines for reaction with:
a. Reaction with an active ester: Find a solvent in which active ester is soluble (methylene chloride is a preferred solvent) and dissolve the ester in the dry solvent, add
triethylamine, then add the amine, either neat or drop wise as a solution in the reaction solvent. Use at least a 10% excess of all reagents relative to the active ester. This
can be carried out at ambient temperatures.
b. Reaction with a free acid: generate the active ester in situ with EDC and NHS or HOBt, then add the triethylamine, followed by the amino-dPEG4 t-butyl ester; or ii)
combine the acid, NHS or HOBt, TEA, and the amino-dPEG®4 t-butyl ester, and add a solution of the EDC. Use at least a 10% excess of reagents relative to the acid.
Note: Carbodiimides other than EDC can be used, but the water soluble and polar nature of the by-products makes work-up very efficient with EDC. DCC is also very good,
if one is able to remove all of the DCU. These reactions are best carried out at –10 - 0° C. The reactions all need to be monitored by chromatography, TLC, or HPLC.
DPG-5714-PI
100 mg
500 mg
(M.W. 497.62)
1g
H2N
O
O
O
O
O
O
O
O
O
O
10271
DPG-5716-PI
100 mg
500 mg
(M.W. 673.83)
1g
H2N
O
O
O
O
O
O
O
O
O
O
O
O
O
O
DPG-5718-PI
100 mg
10281
4 °C 89 Angstroms and 76 atoms spacer (nitrogen to carbonyl carbon)
1g
(M.W. 1202.46)
A carboxy protected dPEG®x amino acid pegylation reagent, dPEG® pegylation spacer
and modifier with a reactive amine and a t-butyl protected carboxylic acid
H2N
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
10311
Order Hotline 1-800-777-4779 502-266-8787
3
PRODUCT
CodeQty
Methoxy Terminated Amine Reactive Reagents
Makes discrete MW pegylation modification possible with our unique range of m-dPEG® pegylation NHS esters.
m-dPEG® pegylation produces compounds with increased water solubility and reduced aggregation, also reduces immunogenicity and potentially even toxicity.
Can be used in conjunction with amino protected amino dPEG® acids for the pegylation of surfaces for produce hydrophilic and reactive.
surfaces with no non-specific binding issues.
Allows for low MW discrete pegylation of small molecule drugs and other related compounds for increased water solubility and reduced aggregation,
or of surfaces to reduce non-specific binding; may even be useful for “dusting” enzymes and other proteins to increase chemical stability.
Amine reactive.
Produces stable amide bond.
General Protocol for modification:
The amount of the m-dPEG®x NHS ester used in the modification reaction is potentially going to depend on several variables, including, a) the modification application, e.g., solution or surface, organic or aqueous, large biological or small organic, b) the concentration of the specific reactive amines available for reaction, as well as
c) the desired effect from the m-dPEG® which is incorporated. In this latter case, choosing the proper value of x will be important, and this may involve experimenting
with a range of values, currently from x = 2 to 24, as well as a tribranched compound with a discrete MW over 2200 D. Therefore, one needs to take at least these vari ables into consideration before a basic optimization experiment is designed and run.
m-dPEG®x NHS Pegylation modification reaction protocol:
a) For aqueous based modifications the reaction can be run in an amine-free buffer at pH 7-8. The m-dPEG® NHS ester can be added as a stock solution in a dry
organic solvent such as DMAC (recommended), DMSO or DMF. This stock solution can be stored for several months frozen at –20° C, if care is taken to exclude mois-
ture in the preparation and handling of the NHS ester. The calculated amount of the stock is added to the aqueous reactant solution and the reaction will be complete in
about 30 minutes to about 2 hours, depending on the specific stoichiometry of the reaction and the desired extent of reaction. The half-life of the NHS ester at pH 8 and
4° C is about 60 minutes. Use your established methods to monitor the reaction.
b) For organic based modifications one uses standard organic procedures, generally adding a solution of the m-dPEG® NHS ester to a solution of the reactant containing a tertiary amine, e.g., Hünig’s base, triethylamine. Homogeneous reactions are typically monitored by TLC or HPLC. Where possible we recommend using methyline chloride as the reaction solvent, which also greatly facilitates the work-up, however, if the solubility of the compound to be modified will not allow this, use other appro-
priate solvents like DMF or DMAC. Optionally, the reaction can be run as a slurry and the reaction will “pull” the reactants into solution, as the incorporated dPEG® will
greatly increase the solubility in many organic solvents, but especially methylene chloride.
•
•
•
•
•
•
m-dPEG® 2-NHS Ester(MW = 245) DPG-5719-PI
100 mg
4 °C 500 mg
Methoxy-dPEG®-N-Hydroxysuccinimide (MW=245) 8.5 Angstroms and 8 atoms spacer
1g
(M.W. 245.23)
Can be used in conjunction with amino protected amino dPEG® acids for the pegylation
O
of surfaces for produce hydrophilic and reactive surfaces with no non-specific binding issues
O
O
N
CH3O
O
O
m-dPEG®4-NHS Ester (MW = 333)
DPG-5720-PI
100 mg
4 °C 500 mg
1g
O
(M.W. 333.33)
10327
H3CO
O
O
O
O
O
N
O
10211
m-dPEG®
DPG-5723-PI
100 mg
8-NHS Ester(MW = 509)
4 °C 500 mg
(M.W. 509.54)
O
Amine Reactive
O
O
O
O
O
CH3O
O
O
O
N
Makes discrete MW pegylation modification possible with
O
our unique range of m-dPEG® pegylation NHS esters
O
DPG-5725-PI
10260100 mg
4 °C Methoxy-dPEG®-N-Hydroxysuccinimide (MW=685) 1g
44.0 Angstroms and 38 atoms spacer O O
CH O
O
O
O
N
(M.W. 685.75)
O
O
O
O
O
O
O
O
O
Amine Reactive
O
3
10262
4
Order Hotline 1-800-777-4779 502-266-8787
PRODUCT
CodeQty
DPG-5727-PI
100 mg
4 °C Methoxy-dPEG®-N-Hydroxysuccinimide (MW=1214) 500 mg
86.2 Angstroms and 74 atoms spacer
1 g
(M.W. 1214.39)
Amine Reactive
Makes discrete MW pegylation modification possible with our unique range of m-dPEG® pegylation NHS esters
O
CH3O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
N
O
m-dPEG® -Acids
• Acid form of the corresponding m-dPEG® NHS esters
• Can activate the acid in situ using standard activation methods, e.g., with EDC and NHS in methylene chloride (see protocol)
• Pegylation spacer is water soluble, non-immunogenic and non-toxic, so can be used to modulate the properties of the m-dPEG® pegylation modified compounds.
10304
reagents under dry conditions. Stir for several hours or overnight, then evaporate the solvent and use. Can also treat reaction mixture with a small amount of silica gel to
adsorb the excess EDC and the urea by-product, filter, then evaporate the solvent and use. Note of caution: The NHS should be added with the EDC to prevent formation of the anhydride. DCC can also be used. Typically use about 1 equivalent, and add a solution of the DCC to the acid and NHS (1.1 to 1.2 equivalents).
HOBt or PFP (2,3,4,5,6-pentafluorophenol) could be used in place of the NHS, if this is a preference for the activated ester. Others too can be used as well, but these are
probably the most popular. If one wanted to make the sulfo-NHS ester, then a much more polar solvent would be needed to accommodate the very poor solubility of the
sulfo-NHS in organic solvents, using solvents such as DMF or DMAC.
m-dPEG®4 -Acid (MW = 236)
DPG-5721-PI
250 mg
4 °C Methoxy-dPEG® (MW=236) 1g
(M.W. 236.26)
Acid form of NHS Ester, DPG-5720-PI
O
OH
O
Pegylation spacer is water soluble, non-immunogenic and non-toxic, so can be used
O
H3CO
O
to modulate the properties of the m-dPEG® pegylation modified compounds
10234
m-dPEG®2 -Acid (MW = 148)
DPG-5722-PI
100 mg
4 °C 8.5 Angstroms and 8 atoms spacer 500 mg
(M.W. 148.16)
1g
O
Pegylation spacer is water soluble, non-immunogenic and non-toxic, so can be used
CH3O
®
O
OH
to modulate the properties of the m-dPEG pegylation modified compounds
10326
m-dPEG®8-Acid (MW = 412)
DPG-5724-PI
100 mg
(M.W. 412.47)
O
CH3O
O
O
O
O
O
O
OH
O
10324
m-dPEG®24-acid (MW = 1117)
DPG-5728-PI
100 mg
4 °C Methoxy-dPEG®-N-Hydroxysuccinimide (MW=1117) 500 mg
1 g
(M.W. 1117.31)
Pegylation spacer is water soluble, non-immunogenic and non-toxic, so can be used to
modulate the properties of the m-dPEG® pegylation modified compounds
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
OH
10339
Order Hotline 1-800-777-4779 502-266-8787
5
PRODUCT
CodeQty
Carboxyl-dPEG®4-(m-dPEG®12)3 Ester
DPG-5730-PI
100 mg
4 °C (M.W. 2323.73)
1g
Amine reactive pegylation reagent with a tribranched dPEG®4 branch; activate carboxylic acid in situ
CH3O
O
O
O
O
O
O
O
O
H
N
O
O
O
O
O
O
O
O
O
O
O
O
O
O
N
H
O
O
CH3O
O
O
O
O
O
O
O
O
O
O
O
O
N
H
O
O
O
O
O
N
H
O
CH3O
O
O
OH
H
N
O
O
•
•
•
•
•
•
Single compound; made synthetically from 99.5% pure tetraethylene glycol.
Imparts significant and surprising water solubility, and the modifier itself is non-immunogenic and non-toxic.
Potentially very useful as a drug modifier with high hydrodynamic volume.
Produces compounds with reduced aggregation, or surfaces with reduced non-specific binding.
Produces stable amide bond.
Activate in situ with EDC/NHS.
10402
Methoxy Terminated Carbonyl / Carboxyl Reactive Reagents
• Carbonyl/carboxyl reactive dPEG®; this unique pegylation reagent reacts with acids, active esters and aldehydes.
• Each is a single compound; made from 99.5% pure tetraethylene glycol.
• In modification reactions: Pegylation arm imparts significant and surprising water solubility, and the modifier itself is non-immunogenic and non-toxic, so can
decrease these properties in the modified application.
• For surface applications: m-dPEG® amine pegylation reagent will react on surfaces to significantly reduce or eliminate non-specific interactions and create
a monolayer surface structure. Can be used in conjunction with the amino dPEG® acids or amino dPEG® esters to protect the surface as well as to impart
functionality back to a carboxylated surface.
General guidelines for use: In all cases care should be taken in handling the materials, they are amines. All are very hygroscopic and will react with the atmosphere
over time, so should be handled accordingly. For weighing purposes, dPEGx, x < 12 can be handled as liquids, x > 12 are nice solids when kept cool or cold. X =
12 can be easily melted and treated as a liquid. Again, these are amines and should be treated accordingly.
Organic media reactions: The amines are soluble in all organic solvents of moderate to higher polarity. We prefer methylene chloride or DMAC. The amines are
easily reacted with acids activated in situ or with active esters, like HOBt (and derivatives), PFP or NHS, using a tertiary amine to help drive the reaction to completion.
Aqueous media: The acid can be activated with EDC and sulfo-NHS, then reacted with the m-dPEG® amine pegylation reagent. This is best done in a non-amine
containing buffer, e.g., in MES buffer at pH 5-6, raise the pH to between 7.2 to 7.5 with phosphate buffer just before reacting with the amine or after the amine has
been added.
See Hermanson chapter 3, pp. 215-233 for more details and sample protocols.
Reference:
Greg T. Hermanson, Bioconjugate Techniques, 2nd Ed, Elsevier Inc., Burlington, MA 01803, April, 2008 (ISBN-13: 978-0-12-370501-3; ISBN-10: 0-12-370501-0). Specifically, see pp. 726-729, Chapter 18, on discrete PEG compounds for pegylation applications.
m-dPEG®4 Amine DPG-5731-PI
100 mg
4 °C 15.5 Angstroms and 14 atoms spacer
500 mg
(M.W. 207.27)
1 g
Carbonyl/carboxyl reactive dPEG®; this unique pegylation reagent reacts with acids, active esters and aldehydes.
O
O
CH3O
O
NH2
100
mg
10175
1g
(M.W. 383.48)
CH3O
O
O
O
O
O
O
O
NH2
100 mg
10278
1g
(M.W. 559.69)
O
CH3O
O
O
O
O
O
O
O
NH2
O
O
O
10288
6
Order Hotline 1-800-777-4779 502-266-8787
PRODUCT
CodeQty
100 mg
1g
(M.W. 1088.32)
Carbonyl/carboxyl reactive dPEG®; this unique pegylation reagent reacts with acids, active esters and aldehydes
CH3O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
NH2
O
Surface Reactive and Thiophilic Reagents
10318
• Thiol
is reactive with metal surfaces, other thiols, disulfides, maleimides, vinyl sulfones,and haloacetamides
and incorporates the pegylation spacer into all of these various functionality.
• dPEG® pegylation spacer is hydrophilic, highly water soluble, and non-immunogenic.
Thiol-dPEG®4 Acid DPG-5735-PI
100 mg
1g
(M.W. 282.35)
Bifunctional thiol acids with dPEG® pegylation spacer
HS
O
O
O
O
OH
O
10247
•
•
•
•
•
•
Bifunctional thiol acids with dPEG® pegylation spacer.
Once functionalized, the carboxylic acid moiety can be activated for further reaction, e.g. with EDC/NHS.
Potentially activatable carboxylic acid moiety.
Product handling and stability:
Keep product under an inert atmosphere to prevent oxidation to the disulfide; though the dPEG® thiol acids do not seem to be highly prone to oxidation.
Product is very soluble in methylene chloride and ethyl acetate, and is itself only slightly soluble in water as the acid. However, once reacted the hydrophilicity
of the dPEG® pegylation spacer is imparted.
Thiol-dPEG®8 Acid DPG-5737-PI
100 mg
500 mg
(M.W. 458.57)
1g
Bifunctional thiol acids with dPEG® pegylation spacer
O
O
O
HS
• Incorporates the dPEG® carboxylic acid.
• Potentially activatable carboxylic acid moiety.
• Once functionalized, the carboxylic acid moiety can be activated for further reaction, e.g. with EDC/NHS.
O
O
O
O
O
O
OH
Thiol-dPEG®4 t-Butyl Ester DPG-5736-PI
100 mg
10183
4 °C (M.W. 338.46)
500 mg
Thiol and protected acid bifunctional reagent with unique dPEG® spacer
1g
• Thiol and protected acid bifunctional reagent with unique dPEG® spacer.
• t-Butyl group is easily removed with TFA (25% TFA in CH2Cl2, ice bath/0° C, about 5 h)
and provides a potentially powerful purification handle.
O
O
HS
O
O
O
O
Hydroxy-dPEG®4 t-Butyl Ester DPG-5738-PI
1g
10248
(M.W. 322.39)
Surface Modification Reagent with Free Alcohol
•
•
•
•
HO
O
O
Surface modification reagent with free alcohol, which can be reacted with activated surfaces
or converted to another reactive functionality.
Potentially useful in oligo modification - see Oligonucleotide modifiers.
A flexible pegylation reagent with a free hydroxyl which can be converted to a functionality of choice.
dPEG® pegylation spacer is hydrophilic, water soluble and non-immunogenic, and will incorporate these properties into any application.
O
O
O
O
10223
Hydroxy-dPEG®8 t-Butyl Ester DPG-5796-PI
100 mg
1g
(M.W. 498.60)
Surface Modification Reagent with Free Alcohol
•
•
•
•
•
Can be used to make a variety of other functional dPEG® based reagents
Surface modification reagent with free alcohol, which can be reacted with activated surfaces or converted to another reactive functionality.
Potentially useful in oligo modification - see Oligonucleotide modifiers
A flexible pegylation reagent with a free hydroxyl which can be converted to a functionality of choice.
dPEG® pegylation spacer is hydrophilic, water soluble and non-immunogenic, and will incorporate these properties into any application.
Order Hotline 1-800-777-4779 502-266-8787
PRODUCT
CodeQty
Miscellaneous Reagents
DPG-5739-PI
100 mg
O-Benzyl-dPEG®4 Acid M. Bodanszky and A. Bodanszky, The Practice of Peptide Synthesis, pp. 129-134, 2nd Ed., Springer-Verlag, Berlin Heidelberg, (1994). This reference contains specific protocols.
P.J. Kocienski, Protecting Groups, pp. 46-49, Georg Thieme Verlag, Stuttgart, (1994).
O
O
O
•
•
•
Amine reactive carboxylic acid dPEG® pegylation modifier/spacer; with protected hyroxyl.
Pegylation spacer is the highly water soluble and non-immunogenic discrete dPEG®.
Benzyl protecting group is acid and base-stable and removable with simple Pd/C reduction
or via transfer hydrogenation for better functional group selectivity.
O
O
O
OH
10233
Heterobifunctional dPEG® Crosslinkers
Our dPEG® pegylation version of the popular SATA reagent, providing a method for converting the amino group to a thiol with the incorporation of the pegylation unit
• Adds the properties of dPEG®, including added pegylation spacer distance, a spacer that is highly hydrophilic, non-antigenic, non-immunogenic and non-toxic
• Greater accessibility of reaction/modification site, i.e., spacer distance makes the amine, now thiol, much more accessible, e.g., a maleimide, vinyl sulfone or a α-halo
keto functionalize reaction partner.
Protocols:
Using conditions similar to those used for SATA to remove the acetyl protecting group can be applied for the dPEG®4 SATA.
4 °C 18 Angstroms and 16 atoms spacer
500 mg
(M.W. 356.41)
1g
Amine reactive Carboxylic Acid dPEG® pegylation modifier/spacer; with Protected Hydroxyl
MAL-dPEG®4-Acid
DPG-5763-PI
100 mg
Mol. Wt.: 416.42; single compound
17.5 Angstromsand 16 atomsspacer
Pegylation Crosslinker Reagent with Amine and Sulfhydryl / Thiol Reactivity
4 °C
1000 mg
• Activate the carboxyl in situ with EDC/NHS or other activation chemistry of the carboxylic acid
S-Acetyl-dPEG®4 Acid (dPEG®4 SATA Acid) DPG-5741-PI
100 mg
500 mg
(M.W. 324.39)
1g
O
O
O
S
O
O
O
OH
S-Acetyl-dPEG®8 Acid (dPEG®8 SATA Acid) DPG-5742-PI
100 mg
4 °C 10180
500 mg
(M.W. 500.60)
1g
O
O
S
O
O
O
O
O
O
O
O
OH
• This acid form needs to be activated in sita to some form of active ester.
10182
S-Acetyl-dPEG®4 NHS Ester (dPEG®4 SATA) DPG-5740-PI
100 mg
500 mg
(M.W. 421.46)
1g
O
O
O
S
O
O
O
O
O
N
O
S-Acetyl-dPEG®8 NHS Ester (dPEG®8 SATA) DPG-5743-PI
100 mg
4 °C 10181
1g
(M.W. 597.67)
O
O
S
O
10184
O
O
O
O
O
O
O
O
O
N
O
Order Hotline 1-800-777-4779 502-266-8787
PRODUCT
CodeQty
Mono-N-t-Boc-Amido-dPEG®
•
•
•
Convenient mono-protected dPEG diamine for pegylation -- selectively react just one end, then subsequently deprotect
with TFA to make other amine available for reaction
Hydrophilic, non-immunogenic dPEG® pegylyation spacer
Water soluble with pegylation spacer
Mono-N-t-Boc-Amido-dPEG®3 Amine DPG-5744-PI
500 mg
4 °C 15 Angstroms and 16.9 atoms spacer
1g
(M.W. 320.43)
O
N
H
O
O
O
O
NH2
Mono-N-t-Boc-Amido-dPEG®11 Amine DPG-5745-PI
100 mg
10225
1g
(M.W. 644.79)
H
N
O
O
O
O
O
O
O
O
O
O
O
NH2
O
O
Mono-t-Boc-1,6-Diaminohexane DPG-5746-PI
1g
10172
4 °C
(M.W. 216.32)
.
O
NH2
N
H
O
Mono-N-Cbz-Amido-dPEG®3 Amine DPG-5747-PI
500 mg
1g
(M.W. 354.44)
Introduces a 15 atom and 16.9 Angstrom hydrophilic, non-immunogenic dPEG® pegylation spacer
10176
O
N
H
O
O
O
O
NH2
10269
dPEG® Peptide Synthesis Reagents with Spacers
Fmoc-Based Solid Phase Synthesis
DPG-5748-PI
1g
Fmoc-Amido-dPEG®2 Acid 4 °C 10.9 Angstroms and 10 atoms spacer
5g
(M.W. 399.44)
Peptide pegylation reagent, Fmoc protected dPEG® amino acids
H
N
O
OH
O
O
O
O
10243
Fmoc-Amido-dPEG®4 Acid DPG-5749-PI
100 mg
(M.W. 487.54)
5g
H
N
O
O
O
O
O
OH
O
O
100 mg
1g
10213
(M.W. 575.65)
5g
N-Fmoc protected hydrophilic, non-immunogenic spacer
H
N
O
O
O
O
O
O
OH
O
O
O
10063
8
Order Hotline 1-800-777-4779 502-266-8787
7
PRODUCT
CodeQty
100 mg
(M.W. 663.75)
H
N
O
O
O
O
O
O
O
OH
O
O
O
O
Fmoc-Amidoxy-dPEG®12 Acid DPG-5795-PI
100 mg
10273
4 °C (M.W. 855.96)
Fmoc-N-Amido-dPEG®12 Acid DPG-5752-PI
100 mg
H
(M.W. 839.96)
O
OH
O
O
O
O
O
N
O
O
O
O
O
O
O
O
O
100 mg
10283
4 °C 89 Angstroms and 76 atoms spacer 1g
(M.W. 1368.59)
Peptide pegylation reagent, Fmoc protected dPEG® amino acids, Useful for incorporating all of the
wonderful properties of a dPEG®, either as a spacer in or terminating group of the peptide sequence
H
N
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
OH
O
O
O
Cbz-Based Solid Phase Synthesis
DPG-5754-PI
100 mg
Cbz-Amido-dPEG®4 Acid 4 °C 19.2 Angstroms and 17 atoms spacer 1g
(M.W. 399.44)
10313
N-Cbz protected hydrophilic, non-immunogenic spacer
H
O
N
O
O
O
O
OH
O
O
10268
Cbz-Amido-dPEG®6 Acid DPG-5755-PI
100 mg
(M.W. 487.54)
O
O
N-Cbz protected hydrophilic, non-immunogenic spacer
O
O
O
O
N
H
OH
O
O
O
100 mg
4 °C 10066
32.2 Angstroms and 28 atoms spacer 1g
(M.W. 575.65)
H
O
N
O
O
O
O
OH
N-Cbz Protected Hydrophilic, Non-Immunogenic Spacer
O
O
O
O
O
O
Cbz-Amido-dPEG®12 Acid DPG-5757-PI 100 10276
mg
(M.W. 751.86)
N-Cbz Protected Hydrophilic, Non-Immunogenic Spacer
H
N
O
O
O
O
O
O
O
O
O
O
O
O
O
OH
O
O
100 mg
4 °C 10286
88.5 Angstroms and 76 atoms spacer 1g
(M.W. 1280.49)
N-CBZ protected dPEG® amino acid pegylation reagents for peptide synthesis
H
N
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
OH
O
O
O
O
O
O
O
O
O
O
O
O
10316
Order Hotline 1-800-777-4779 502-266-8787
PRODUCT
CodeQty
Merrifield Boc-Based Solid Phase Synthesis
DPG-5759-PI
100 mg
t-Boc-Amido-dPEG®4 Acid PEPTIDES INTERNATIONAL
(M.W. 365.42)
5g
N-t-Boc Protected Hydrophilic, Non-Immunogenic Spacer
H
O
N
O
O
O
O
OH
O
•
•
•
•
O
N-t-boc protected dPEG® amino acid pegylation reagents for peptide synthesis.
Useful for incorporating all of the wonderful properties of a dPEG®, either as a spacer in or terminating group of the 10220
peptide sequence.
Pegylation spacer incorporates water solubility, reduces or eliminates aggregation, and is inherently non-immunogenic and non-toxic.
Bulk pricing available, please inquire.
Thiol Modifiers
•
•
•
•
•
Useful pegylation reagents for incorporating the sulfhydryl moiety into a peptide, that contains the dPEG® pegylation unit.
Potentially a significant alternative to cysteine for incorporating the sulfydryl into peptides.
Useful for incorporating all of the wonderful properties of the dPEG®, either as a spacer or terminating group in the peptide sequence.
Pegylation spacer incorporated water solubility, reduces or eliminates aggregation, and is inherently non-immunogenic and non-toxic.
Bulk pricing available, please inquire.
Trityl-S-dPEG®4 Acid DPG-5760-PI
100 mg
(M.W. 524.67)
1g
O
O
S
OH
O
10300
• Pegylation reagent incorporates a dPEG® chain of 16 atoms and 18.3 Å in length.
• Trityl is removed using 25-50% TFA with 5% TIS (triisopropyl silane).
Methoxytrityl-S-dPEG®4 Acid DPG-5761-PI
100 mg
(M.W. 554.70)
1g
S
O
O
OH
O
O
O
10301
OCH3
• Mmt can be removed with <5% TFA in the presence of TIS (triisopropyl silane).
Methoxytrityl-S-dPEG®8 Acid DPG-5762-PI
100 mg
(M.W. 730.91)
1g
O
S
O
O
O
O
O
O
O
OH
O
CH3O
• Mmt can be removed with <5% TFA in the presence of TIS (triisopropyl silane).
10166
Hydroxyl Modifiers
O-Benzyl-dPEG®4 Acid DPG-5739-PI
100 mg
4 °C 18 Angstroms and 16 atoms spacer 500 mg
(M.W. 356.41)
1g
M. Bodanszky and A. Bodanszky, The Practice of Peptide Synthesis, pp. 129-134, 2nd Ed., 1994, Springer-Verlag, Berlin Heidelberg. This reference contains specific protocols.
P.J. Kocienski, Protecting Groups, pp. 46-49, 1994, Georg Thieme Verlag, Stuttgart.
O
Amine reactive CARBOXYLIC acid dPEG® pegylation modifier/spacer; with protected Hyroxyl.
10233
Pegylation spacer is the highly water soluble and non-immunogenic discrete dPEG®
Benzyl protecting group is acid and base-stable.
Benzyl group removable with simple Pd/C reduction or via transfer hydrogenation for better functional group selectivity.
12
O
O
Order Hotline 1-800-777-4779 502-266-8787
O
O
O
O
O
OH
Order Hotline 1-800-777-4779 502-266-8787
Order Hotline 1-800-777-4779 502-266-8787
Notes
Order Hotline 1-800-777-4779 502-266-8787
Order Hotline 1-800-777-4779 502-266-8787
All About Ordering...
Confirming Orders
Please mark all confirming orders clearly to avoid duplication.
Back Orders
Should an item be temporarily out of stock, this will be indicated in the “back order” column of the
customer’s invoice. Most back orders are shipped within two weeks or less.
Prices
All prices are stated in U.S. dollars and are subject to change. However, any item whose price has risen
more than ten percent from that listed in our current catalog will not be shipped without customer authorization.
Terms
Net 30 days; in some cases full or partial pre-payment may be required.
Shipping
Prices are CPT Destination (Carriage Paid To, Incoterms 2000), with shipping charges prepaid and added
to the invoice. Most purchase orders are processed the same day they are received and are shipped by
FedEx overnight or second day service, or your preferred carrier. Should you require even faster service,
any order placed before 3:00 PM Eastern Time can be shipped overnight (next day air service). This
results in guaranteed U.S. delivery the very next morning. For most orders outside of the U.S., please
contact us for shipping details.
Returns
If there is ever a problem with your order, please contact us immediately for return shipping instructions
and to receive an authorization for return. All returns must be made within thirty days of receiving your
order. We do reserve the right to charge a fee on returned goods due to an ordering error.
Liability
All products sold by Peptides International, Inc. are intended solely for experimental use and are not
intended for use in or on human subjects. User assumes all risk of patent infringement by reason of use
of material provided by Peptides International. Peptides International cannot be responsible for damages
arising from misuse of any product.
Order Hotline 1-800-777-4779 502-266-8787
Bulk Pricing
Discounts on many bulk and large orders are available through our technical sales department. Such
orders are issued a personal quote number. Reference to this quote number will enable us to serve you
even more quickly when ordering in the future.
Minimum Orders
Peptides International does not require a minimum order.
Ordering is easy!
Our customer service representatives are ready to help you process your orders, assist you with product information, and to answer your technical questions. Orders can be placed by mail, telephone, fax, e-mail, or by
using our order hotline (800-777-4779 USA and Canada).
The easiest way is for you to simply send an email or fax with your P.O. Number (payable in US Currency).
Please include contact information and preferred shipping method . Our suggested shipping method is FedEx
international, and for most European countries a typical small box costs $30 USD. Also, we accept American
Express, Visa, and Mastercard for your convenience.
You will, of course, be provided a specific quotation upon request. Please contact our technical sales department by email ([email protected]).
We know your time is valuable, and we will always abide by the golden rule to treat you as we would like to
be treated.
ORDER HOTLINE
800-777-4779 (US and Canada)
ORDER VIA EMAIL
[email protected]
MAILING ADDRESS
Peptides International, Inc.
P. O. Box 99703
Louisville, Kentucky 40269-0703 USA PHYSICAL ADDRESS
11621 Electron Drive
Louisville, Kentucky 40299 USA
HOURS OF OPERATION
8:30 AM — 6:00 PM EST Monday -Thursday (NY time)
8:30 AM — 5:00 PM EST Friday (NY time)
TELEPHONE
1 (502) 266-8787 or 800-777-4779 (Toll Free US and Canada)
FAX
1 (502) 267-1FAX (1329) 24 Hour Service
EMAIL
[email protected]
WEB SITE
Customers in the following countries should order directly from:
In The Benelux Countries:
In Switzerland:
In Japan:
http://www.peptide.co.jp
Osaka, Japan
Email: [email protected]
http://www.peptide.co.jp
10
Order Hotline 1-800-777-4779 502-266-8787
Lucerne, Switzerland
http://www.lubio.ch/
Huissen, The Netherlands
http://www.bio-connect.nl/
Excellence Compounded.
11621 Electron Drive
Louisville, KY 40299 USA
Phone: +1-502-266-8787
Phone: +1-800-777-4779
Fax: +1- 502-267-1329
Web: WWW.PEPNET.COM
CATALOG PRODUCTS
• RGD Platform
• ProTx-II & Other Toxins
• Biologically Active Peptides
• Substrates & Inhibitors
• dPEGs and Linkers
Full list @ PEPNET.COM
CUSTOM CHEMISTRY SERVICES
Made in USA
• Design Consultation
• Chemistry Development
• Process Scale-up
• Pilot-Scale Synthesis
• Solution & Solid Phase
• Substrates by DesignTM
TM
Key literature citations and patents
referring to Peptides International
products and services
EXCELLENCE COMPOUNDED
• High Purity, Quality and Value
• Strict Confidentiality
• Friendly Service
• Proactive Project Management
PEPNET.

discrete PEGs - Peptides International

Transcription

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