High Field NMR

High Field NMR:
Sixty Years of Cost Effective Solutions to
Real Problems Across Disciplines.
Hz
October 2009, prepared by the project leaders of the CNRS TGE RMN
“In the past increased magnetic fields have always led to new, often unexpected,
domains of application for NMR”
Preamble
toral and postdoctoral training program, and conThe national multidisciplinary delocalised TGE/
tribute to the formation of a new generation of
TGIR for high-field NMR provides the environspectroscopists with a broad interdisciplinary
ment necessary for the efficient development of
knowledge of diverse aspects of biological or matestate-of-the-art NMR and its application to the
rials NMR. In the first year of activity, the infraresolution of important materials, biological and
structure has given access to more than 75 projects
medical problems. The TGE is today comprised of
from more than 50 different national Laboratories.
six sites: Bordeaux, Gif-sur-Yvette, Grenoble,
A Brief history of NMR
Lyon, Lille, Orléans, and gives access to a unique
Since its discovery in 1945, NMR has experienced
range of equipment including high resolution specastonishing technical development, motivated by
trometers operating at multiple fields up to 1 GHz,
the wide range of problems that it can be used to
and supported by technical expertise, and research
address, ranging from physics to medicine. For exgroups dedicated to the development and applicaample, it is currently the only technique capable of
tion of novel, state-of-the-art spectroscopic and
determining protein structures in solution, which
computational methodology in NMR. This infrai m m e d i a t e l y h i g hstructure, equipped with
lights the strategic imthe highest available
portance of this kind
three-dimensional structures of
fields, offers a unique enof spectroscopy today.
vironment to the scienproteins in solution
Its application is howtific community in
In 1986, using NMR,
the group led by
ever by no means limEurope for the study of
Wütrich determined
ited to structural bioldiverse problems in bioa protein structure in
ogy, as it can be used
logical, chemical, physisolution for the first
to study molecular
cal, and medical sciences
time. In 2000 he was
the first to determine
systems relevant to
by NMR. The centers
the structure of a
agriculture (e.g. pestimaking up the TGE also
human prion protein. In 2002 he wins the Nobel
cides), chemical and
propose an extensive docPrize for Chemistry.
materials problems
1
research groups around the world
(notably with the development of
insoluble Alzheimer’s proteins determined
Fourier transform NMR and
by MAS NMR
multi-dimensional techniques,
In the 1960s, the work of Andrew,
leading to the award of the 1991
Waugh, Pines, Stejskal and Shaeffer,
Nobel prize in chemistry to Richprovides high resolution spectra from
solids spinning at the magic angle. From
ard Ernst), as well as by techno1994 onwards Griffin (MIT) provides inlogical developments in probe and
creasingly detailed evidence for the
magnet design. Indeed the pure
functional mechanisms in the memfact that magnet strengths have
brane proteins rhodopsin and bacteriorhodopsin, shining light on the primary steps in vision; in 2002
gone from about 0.9 T (or 40
Tycko (NIH) uses MAS NMR techniques to provide the first strucMHz for protons) in the early
ture of the plaque forming amyloid proteins responsible for Alzdays to 1 GHz today has been one
heimer’s disease; and in 2006 Baldus (Gottingen) shows prelimiof the principal motors for develnary three-dimensional structures for membrane incorporated proteins obtained from high-filed NMR spectra.
opment. It has allowed us to access progressively more and more
complex systems, thereby extend(zeolites, polymers, liquid crystals, pharmaceutiing the domain of application of NMR (see boxes).
cals, cosmetics….), medical diagnostics, or nanoOne of the most exciting aspects of this domain is
technology, and is even relevant to oil exploration.
that while we are absolutely sure that new fields of
application will be found at higher fields (as has
In fact the potential applications of NMR spectroscopy are currently principally limited by the costs
associated with making available sufficiently high
magnetic fields.
“With increasing magnetic fields
NMR will continue to engender
new, high impact, areas of applications in the future”
Over the years has progressively evolved from a
curiosity driven experiment as a demonstration of
fundamental aspects of the newly introduced quantum theory, into a cornerstone technique for the
always been the case in the past), we cannot predict
characterization of an impressively broad range of
where exactly higher fields will have the most immaterials. Today NMR spectroscopy is a central
pact. The open structure of the TGE/TGIR however
tool in the atomic or molecular level understanding
guarantees that it will continue to be accessible to,
of systems as diverse as metal surfaces, catalysts,
and play a leading role in, these new areas of applipolymers, superconductors, glasses, liquid crystals,
cation.
synthetic intermediates, supramolecular systems,
natural products, drugs, membranes, and proteins,
Research Highlights from the Sites.
to name but a few. As such it has become the cenThe sites making up the infrastructure (Bordeaux,
tral analytical technique, and
has revolutionized our approach to the synthesis of new
magnetic resonance imaging: a clinical tool for
materials, and to the determinadiagnosis.
tion of structure and dynamics
In 1973 Paul Lauterbur uses a high-resolution NMR
spectrometer to provide the first Magnetic Resoin solids and in solution.
nance Image, of two test tubes filled with water. In
2006 this has a become a multi-billion dollar industry, and is the technique of choice for the diagnosis
of many common tumors. In 2003 Lauterbur and
Mansfield win the Nobel Prize in Medecine.
This phenomenal progress has
been driven both by the development of the NMR experiment itself tackled by several
2
Gif-sur-Yvette, Grenoble, Lyon,
Lille, Orléans) are all specialized in
developing the NMR technique itself. The group leaders are all well
established figures in the international NMR community. Much of
their work is related to providing
the technical and methodological
developments at the heart of Nuclear Magnetic Resonance that allow other research groups to make
breakthroughs in applications problems. Nevertheless, they have all
made recent contributions themselves to applications, with high
impact discoveries. These applications areas cover a very wide range,
which is one of the most important
features of this distributed infrastructure. The network provides
services to users in areas ranging
from medical science to physics.
Some examples follow:
new frontiers in
physics: from superconductivity to
quantum computing
range network of motions,
leading to the remarkable observation of a standing wave extending across a beta sheet.
Slow motions are related to
processes such as signal transIn 1945 Bloch
duction and allosteric regulaand Purcell
tion. The group is developing
demonstrate
innovative methods combining
the NMR phenomen to valispectroscopic, computational,
date the
and stable isotope labeling apemerging
proaches for the study of moquantum thelecular systems of increasing
ory. They speculate it could be
a useful method for calibrating
size and complexity, of shortmagnetic fields. They win the
lived molecules, and of intrinsiNobel prize for Physics in
cally unstructured proteins. A
1952. Slichter later uses NMR
particular focus is on the develto provide the first experimental proof of the BCS theory for
opment of fast multidimensional
superconductivity. In 1997
NMR methods which will allow
Gershenfeld and Chuang show
the study of transient structures
that high-resolution NMR can
during real time protein folding
provide the support for multi-bit
quantum computation. In 2001
or other non-equilibrium moNMR provides the first experilecular processes. Highlights
mental demonstration of the
include structural and interacsolution to Shror’s Algorithm.
The Lyon group, working with scition studies on proteins and nonentists at MIT and CPE-Lyon, recoding RNAs involved in the
cently observed intermediates in surface supported
process of viral replication, especially those of humetathesis catalysis that prove the mechanism for
man immunodeficiency virus (HIV), hepatitis C
this industrially vital reaction. They also provided
(HCV) and influenza viruses. Another focus is the
the experimental characterization supporting the
investigation of proteins involved in bacterial cell
capability of a single isolated tantalum atom on a
wall synthesis that represent the most important
surface to cleave molecular nitrogen. In different
targets of actual antibiotics. This work was recently
work, with IBCP-Lyon, they showed for first time
pushed further by exploring the capability of solid
that microcrystalline samples allow NMR to probe
state NMR in order to directly study the bacterial
the details of the water-protein interactions that
cell wall and to screen for interacting proteins.
stabilize protein structures and
control folding and unfolding
metabolism, diagnosis, and personalised
processes. In yet another area, the
healthcare.
Lyon group showed how the
Urine was one of the first complex fluids to be
model animal C elegans could be
studied by NMR. This led to the emergence of
successfully used as a platform to
“metabolomics by NMR.” In the 1990s NMR specstudy functional genetics by NMR
tra are used to determine types of cancer. In 2006
Nicholson and coworkers present results from
in connection with disease.
worldwide epidemiological studies, involving
thousands of subjects, determining environmental
factors affecting the occurrence of diabetes and
high blood pressure in whole populations. This
type of NMR is playing a key role in the emergence of the idea of personalized health care.
The Grenoble group has recently
shown that slow movements along
the backbone in a model protein
are correlated and form a long
3
The Gif-sur-Yvette group has a long term interest
in natively unfolded proteins. They developed new
models for the analysis of solution dynamics in
proteins and elucidated the mechanisms for their
folding upon interaction with biological partners in
biologically relevant examples (actin monomer sequestering…). They also worked on the intimate
relationships between protein primary sequences,
dynamic properties and folding, with potential applications in protein engineering. The structure determination of biomacromolecules (proteins,
DNAs, ARNs…) and the analysis of their complexes with other biomacromlecules and ligands
provided important clues towards the understanding of their biological functions,, that open new
routes towards the development of important
therapeutic agents (anti HIV molecules, antibiotics…).
glasses, new materials, and
nanosciences
Quadrupolar nuclei
have always played
a leading role in
NMR. Since the 90s
oxygen and aluminum NMR studies
have continuously
contributed to
change the understanding we have of the structure and dynamics
of glass forming materials and their related molten state. This is now changing the whole way
we think about the formation and structure of
disordered materials. In 2006 Grey and coworkers use understanding from NMR observations directly to improve the charging rate capacity of lithium nickel magnanese oxide in rechargeable batteries.
straints to models. Recent developments now allow
characterization of "molecular motifs" in glasses
allowing to sort out chemical and geometrical disorder at the nanometer scale. They have participated in the characterization of hybrid new materials with specific properties and applications in
nanomaterials, biocompatible materials or drug delivery. Most of these results are obtained in the
course of national and international collaborations.
The Orléans group has developed a world wide
unique laser heating device that allows the investigating of structure and dynamics in the molten
state by NMR up to more that 2000°C, now extending to in-situ measurement of diffusion coefficients. They have also develop new methods for
the characterization of medium range order in
glasses with experimental results that demonstrate
unexpected structural details and add new con-
The Bordeaux group, with scientists at UCSD and
the Burnham Institute in San Diego, succeeded in
reincorporating the Pf1 membrane protein into
biomembranes that are macroscopically oriented by
magnetic fields (biphenyl bicelles), and determined
the topology of the helical protein in the membrane
using nitrogen-proton solid state NMR. In other
work, in collaboration with Cancer Research UK in
London, the fluidity of the nuclear envelope poles
that are involved in male/female cell fusion during
reproduction were measured by deuterium solid
state NMR of live cells. Recently in collaboration
with an INSERM team in Strasbourg who discovered a membranous peptide capable of inhibiting
the development of plasmodium falciparum (malaria), the Bordeaux group was able to propose a
mechanism of action by “molecular electroporation” as inferred from solid sate NMR, molecular
modeling and electrophysiology.
basic chemistry and catalysis
10Å
H
10Å
SiO2
S
E T
O U
E R O
G E N E
The first spectra from catalysts are recorded
in the 1970s, as NMR revolutionizes the way
chemists approach multi-step synthesis. In
2006 Schrock wins the Nobel Prize in Chemistry for his development of meta-thesis,
which has become central to basic industrial
chemistry. In the same year he uses highfield solid-state NMR to validate the mechanism of olefin meta-thesis on a supported
catalyst.
4
The Lille groups develop comsolving the DNA recognition puzzle
plementary approaches in liquid
and solid-state NMR. The two
main groups are working on biological applications (structural
analysis of proteins) and on the
development of solid-state NMR
methods and their applications to
NMR spectra are first obtained from DNA and RNA oligomers in the
inorganic materials. Since 1995,
early 1970s. In 2004, Kaptein uses 900 MHz NMR of protein-DNA
they have introduced many new
complexes to determine the kinetics and structural changes that allow proteins to find their recognition sites in extended DNA sedevelopments for quadrupolar nuquences.
clei concerning both the direct
characterization of quadrupolar
nuclei and the analysis of through-space or
Recent collaboration between Lyon and Orléans
through-bond connectivities with other nuclei.
has led to the development of sophisticated methThese methods are applied to the development of
ods to study the details of structures in complex
17
high-field O NMR characterization of inorganic
inorganic materials, including glasses, including
glasses and ceramics (e.g. sealing glasses for
very advanced ideas about efficient quantum transSOFC, antioxidation phosphate coatings). The bioport in adiabatic processes that was highlighted in
logical NMR group has focused on NMR of hetpress releases around the world.
erogeneous systems, and on proteins involved in
the cell cycle. The group has studied in detail the
Collaboration between Orléans and Lille has reneuronal Tau protein which, upon aggregation, is
cently resulted in three cornerstone publications
one of the molecular hallmarks of Alzheimer’s disdescribing (i) a new probe to study chemical bondease, and has used both solution and High Resoluing differences in alumino-phosphate materials,
tion Magic Angle Spinning NMR to study the
and (ii) a new method to analyze in high-resolution
soluble and aggregated form of the protein.
the connectivities of inorganic fluoride samples.
Frontier domains in NMR: New opportunities at high magnetic fields for the
TGE/TGIR network.
Today we can identify several domains where the
increased availability of high-field NMR is likely
to have considerable impact in the medium term.
These groups already have a history of collaboration. Work between Lyon and Grenoble recently
resulted in the first quantitative analysis of internal
dynamics in a solid protein, and a thesis student is
currently under joint direction. Moreover, the Lyon
and Grenoble sites already jointly operate a European Large Scale Facility, in the context of an Integrated Infrastructure Initiative (www.ralf-nmr.fr).
Obviously, the motor for high-field NMR science
will continue for some years to be structural biology, as it has been for the last 15 years. The
from penicillin to taxol: stereochemistry in the drug industry
O
H
N
H
H
O
In 1959 Karplus proposes a dependence of H-H coupling constants on dihedral angles. Today this forms the basis for the determination of the
stereochemistry of many of the therapeutic drugs on the market, crucial to
S
both their safety and efficiency. Recent developments combining cryoN
cooled probes and high magnetic fields, have made possible the monitoring of enantiomeric purity by NMR of deuterium at natural abundance, usO
O- ing liquid crystalline solvents. This allows the discrimination between enantiomeric forms of compounds which previously could not be resolved.
5
TROSY effect, allowing access to ever larger biological molecules in solution, is predicted to be at
its best at an NMR frequency close to 1 GHz. This
will allow solution-state NMR studies of larger
proteins, and notably allows for the possibility of
Clearly one of the most interesting analytical objectives would be to provide diagnostic and prognostic tools for medical applications through the
analysis of biological fluids, such as urine or
plasma, or biopsy type materials. There has been
some very impressive progress made in this area
over the last ten years, and it is clear that increased
sensitivity will lead to the detection of metabolites
present at lower and lower concentrations, providing reliable markers for diverse diseases.
“ The open structure of the TGE/
TGIR guarantees that it will be accessible to, and play a leading role
in, these new areas of application.”
In conclusion, as in the past, it is clear that NMR
will continue to provide the key to many highimpact problems in multi-disciplinary science in
the future, driven forward to a large degree by the
inexorable increase in magnetic field strengths.
studying membrane proteins in detergent formulations. Also, the study of proteins in the solid state,
whether micro-crystalline, fibril forming, or membrane incorporated, will be increasingly enabled by
the increased sensitivity of higher fields. Greater
accesibilty for NMR studies in such samples will
provide better understanding of the mechanism of
diseases, and yield new perspectives for therapy.
Selected Key References for the Subjects Highlighted in the Boxes.
L.C. Hebel and C.P. Slichter. "Nuclear Spin Relaxation in Normal and
Superconducting Aluminum." Physical Review 1959;113:1504-19.
M. Karplus. "Contact Electron-Spin Coupling of Nuclear Magnetic
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The whole field of nanotechnology and new materials will clearly benefit considerably from increasing magnetic field strengths. The probe nuclei in
these materials are often quadrupolar in nature. The
simplifying effect of high field is absolutely spectacular in these cases, and should allow access to
understanding the molecular level organization and
properties of increasingly complex materials. This
is particularly exciting as it opens up a tool which
will actively aid the development of many new,
high technology, materials.
M. Karplus. "Vicinal Proton Coupling in Nuclear Magnetic Resonance." Journal of the American Chemical Society 1963;85:2870.
P.C. Lauterbur. "Image Formation by Induced Local Interactions Examples Employing Nuclear Magnetic-Resonance." Nature
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P. Mansfield. "Multi-Planar Image-Formation Using NMR Spin Echoes." Journal of Physics C-Solid State Physics 1977;10:L55-L8.
M.P. Williamson, T.F. Havel and K. Wuthrich. "Solution Conformation
of Proteinase Inhibitor-Iia from Bull Seminal Plasma by H-1 Nuclear
Magnetic-Resonance and Distance Geometry." Journal of Molecular
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S.E. Barrett, D.J. Durand, C.H. Pennington, C.P. Slichter, T.A. Friedmann, J.P. Rice and D.M. Ginsberg. "Cu-63 Knight-Shifts in the Superconducting State of Yba2cu3o7-Delta(Tc=90-K)." Physical Review
B 1990;41:6283-96.
I. Farnan, P.J. Grandinetti, J.H. Baltisberger, J.F. Stebbins, U. Werner, M.A. Eastman and A. Pines. "Quantification of the Disorder in
Network-Modified Silicate-Glasses." Nature 1992;358:31-5.
Finally, one of the most exciting areas where
higher fields will have great impact in the long
term is that of basic analytical sciences in general,
and development of analytical methods for medical
diagnosis in particular. Here the principle drawback
of NMR is sensitivity. This of great importance
when considering the analysis of environmental
samples, for example, often only available in trace
quantities. The recent development of microcoil
technology, and “lab on a chip” approaches, combined with high fields will push back the detection
limits, making it possible to analyze increasingly
smaller quantities, with increasing reliability.
B.T. Poe, P.F. McMillan, B. Coté, D. Massiot and J.P. Coutures “Magnesium And Calcium Liquids: In situ High-Temperature 27Al NMR
Spectroscopy,” Science 1993;259:768-88.
A. Meddour, I. Canet, A. Loewenstein, J.M. Pechine and J. Courtieu.
"Observation of Enantiomers, Chiral by Virtue of Isotopic-Substitution,
through Deuterium NMR in a Polypeptide Liquid-Crystal." Journal of
the American Chemical Society 1994;116:9652.
J.G. Hu, R.G. Griffin and J. Herzfeld. "Synergy in the Spectral Tuning
of Retinal Pigments - Complete Accounting of the Opsin Shift in Bacteriorhodopsin." Proceedings of the National Academy of Sciences of
the United States of America 1994;91:8880-4.
N.A. Gershenfeld and I.L. Chuang. "Bulk spin-resonance quantum
computation." Science 1997;275:350-6.
J.G.G. Hu, R.G. Griffin and J. Herzfeld. "Interactions between the
protonated Schiff base and its counterion in the photointermediates of
bacteriorhodopsin." Journal of the American Chemical Society
1997;119:9495-8.
J.F. Stebbins and Z. Xu. "NMR evidence for excess non-bridging oxygen in an aluminosilicate glass." Nature 1997;390:60-2.
6
R. Zahn, A.Z. Liu, T. Luhrs, R. Riek, C. von Schroetter, F.L. Garcia, M.
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P. Felgines Avenier, M. Taoufik, A. Lesage, A. Baudouin, A. De Mallmann, L. Veyre, J.-M. Basset, L. Emsley, and E.A. Quadrelli, “Dinitrogen Dissociation on an Isolated Surface by a Single Tantalum Atom,”
Science 2007; 317: 1056.
L.M.K. Vandersypen, M. Steffen, G. Breyta, C.S. Yannoni, M.H. Sherwood and I.L. Chuang. "Experimental realization of Shor's quantum
factoring algorithm using nuclear magnetic resonance." Nature
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F. Blanc, R. Berthoud, C. Copéret, A. Lesage, L. Emsley, R. Singh, T.
Kreickmann, R.R. Schrock, “Direct observation of reaction intermediates for a well-defined heterogeneous alkene metathesis catalyst,”
Proceedings of the National Academy of Sciences of the United
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J.T. Brindle, H. Antti, E. Holmes, G. Tranter, J.K. Nicholson, H.W.L.
Bethell, S. Clarke, P.M. Schofield, E. McKilligin, D.E. Mosedale and
D.J. Grainger. "Rapid and noninvasive diagnosis of the presence and
severity of coronary heart disease using H-1-NMR-based metabonomics." Nature Medicine 2002;8:1439-44.
Grenoble
G. Bouvignies, P. Bernado, S. Meier, K. Cho, S. Grzesiek, R. Bruschweiler and M. Blackledge, “Identification of slow correlated motions in
proteins using residual dipolar and hydrogen-bond scalar couplings.”
Proceedings of the National Academy of Sciences of the United
States of America 2005;102:13885-90
J.C. Lansing, M. Hohwy, C.P. Jaroniec, A.F.L. Creemers, J. Lugtenburg, J. Herzfeld and R.G. Griffin. "Chromophore distortions in the
bacteriorhodopsin photocycle: Evolution of the H-C14-C15-H dihedral
angle measured by solid-state NMR." Biochemistry 2002;41:431-8.
J.K. Nicholson, J. Connelly, J.C. Lindon and E. Holmes. "Metabonomics: a platform for studying drug toxicity and gene function." Nature
Reviews Drug Discovery 2002;1:153-61.
P. Schanda and B. Brutscher, “Very fast two-dimensional NMR spectroscopy for real-time investigation of dynamic events in proteins on
the time scale of seconds.” Journal of the American Chemical Society
2005;127:8014-5
A.T. Petkova, Y. Ishii, J.J. Balbach, O.N. Antzutkin, R.D. Leapman, F.
Delaglio and R. Tycko. "A structural model for Alzheimer's betaamyloid fibrils based on experimental constraints from solid state
NMR." Proceedings of the National Academy of Sciences of the
United States of America 2002;99:16742-7.
T. Kern, S. Hediger, P. Muller, C. Giustini, B. Joris, C. Bougault, W.
Vollmer and J.P. Simorre, “Toward the characterization of peptidoglycan structure and protein-peptidoglycan interactions by solid-state
NMR spectroscopy.” Journal of the American Chemical Society 2008,
130: 5618.
C.G. Kalodimos, N. Biris, A. Bonvin, M.M. Levandoski, M. Guennuegues, R. Boelens and R. Kaptein. "Structure and flexibility adaptation in nonspecific and specific protein-DNA complexes." Science
2004;305:386-9.
C. Arnero, P. Schanda, M.A. Dura, I. Ayala, D. Marion, B. Franzetti, B.
Brutscher, J. Boisbouvier, “Fast Two-Dimensional NMR Spectroscopy
of High Molecular Weight Protein Assemblies” Journal of the American Chemical Society 2009; 131: 3448.
M.L. Mak, V.S. Bajaj, M.K. Hornstein, M. Belenky, R.J. Temkin, R.G.
Griffin and J. Herzfeld. "Chromophore torsion early in the bacteriorhodopsin photocycle." Biophysical Journal 2005;88:506A-A.
L. Salmon, G.Bouvignies, P. Markwick, N. Lakomek, S. Showalter,
D.W. Li, K. Walter, C. Griesinger, R. Bruschweiler and M. Blackledge,
“Protein conformational flexibility from structure-free analysis of NMR
dipolar couplings : quantitative and absolute determination of backbone motion in ubiquitin,” Angewandte Chemie 2009; 48: 4154.
A.T. Petkova, R.D. Leapman, Z.H. Guo, W.M. Yau, M.P. Mattson and
R. Tycko. "Self-propagating, molecular-level polymorphism in Alzheimer's beta-amyloid fibrils." Science 2005;307:262-5.
F. Blanc, C. Coperet, J. Thivolle-Cazat, J.M. Basset, A. Lesage, L.
Emsley, A. Sinha and R.R. Schrock. "Surface versus molecular siloxy
ligands in well-defined olefin metathesis catalysts:
{(RO)(3)SiO}Mo(=NAr)(=CHtBu)(CH(2)tBu)." Angewandte Chemie
2006;45:1216-20.
Bordeaux
J.G. Beck, D. Mathieu, C. Loudet, S. Buchoux, E.J. Dufourc, “Plant
sterols in "rafts": a better way to regulate membrane thermal shocks”
Faseb Journal, 2007; 21: 1714.
K.S. Kang, Y.S. Meng, J. Breger, C.P. Grey, G. Ceder ”Electrodes with
high power and high capacity for rechargeable lithium batteries, ”Science 2006; 311:977.
S.H. Park, C. Loudet, F.M. Marassi, E.J. Dufourc, and S.J. Opella,
Solid-state NMR spectroscopy of a membrane protein in biphenyl
phospholipid bicelles with the bilayer normal parallel to the magnetic
field. Journal of Magnetic Resonance 2008;193: 133.
T.A. Clayton, J.C. Lindon, O. Cloarec, H. Antti, C. Charuel, G. Hanton,
J.P. Provost, J.L. Le Net, D. Baker, R.J. Walley, J.R. Everett and J.K.
Nicholson. "Pharmaco-metabonomic phenotyping and personalized
drug treatment." Nature 2006;440:1073-7.
M.A. Sani, O. Keech, P. Gardeström, E.J. Dufourc, and G. Gröbner,
Magic-angle phosphorus NMR of functional mitochondria: in situ
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K.A. Henzler-Wildman, M. Lei, V. Thai, S.J. Kerns, M. Karplus, D.
Kern, “A hierarchy of timescales in protein dynamics is linked to enzyme catalysis,” Nature 2007; 450: 913
M. Garnier-Lhomme, R.D. Byrne, T.M.C. Hobday, S. Gschmeissner,
R. Woscholski, D.L. Poccia, E.J. Dufourc, and B. Larijani, Nuclear
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P.J. Sideris, U.G. Nielsen, Z.H. Gan, C.P. Grey, “Mg/Al ordering in
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A. Diller, C. Loudet, F. Aussenac, G. Raffard, S. Fournier, M.
Laguerre, A. Grelard, S.J. Opella, F.M. Marassi, and E.J. Dufourc,
Bicelles: A natural 'molecular goniometer' for structural, dynamical and
topological studies of molecules in membranes. Biochimie 2009; 91:
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Selected Recent References.
Lyon
A. Lesage, L. Emsley, F. Penin and A. Böckmann, “Investigation of
Dipolar-Mediated Water-Protein Interactions in Microcrystalline Crh by
Solid-State NMR Spectroscopy” Journal of the American Chemical
Society 2006; 128: 8246.
Gif-sur-Yvette
B. Elena, G. Pintacuda, N. Mifsud and L. Emsley, “Molecular Structure
Determination in Powders by NMR Crystallography from Proton Spin
Diffusion,” Journal of the American Chemical Society 2006; 128:
9555.
F. Ochsenbein, R. Guerois, J-M. Neumann, A. Sanson, E. Guittet and
C. Van Heijenoort, “Model based on a Lorentzian distribution of correlation times : reconsidering the interpretation of the 15N relaxation
parameters in the case of unfolded proteins.” Protein Science
2002;11:957.
B.J. Blaise, J. Giacomotto, B. Elena, M.-E. Dumas, P. Toulhoat, L.
Ségalat and L. Emsley “Metabotyping of Caenorhabditis elegans reveals latent phenotypes,” Proceedings of the National Academy of
Sciences of the United States of America 2007; 104: 19808.
M. Hertzog, C. Van-Heijenoort, D. Didry, M. Gaudier, J. Coutant, B.
Gigant, G. Didelot, T. Preat, M. Knossow, E. Guittet and M.F. Carlier,
“The b-thymosin/WH2 domain : Structural basis for the switch from
inhibition to promotion of actin assembly.” Cell 2004;117:611.
7
C. Gaudin, M-H. Mazauric, M. Traikia, E. Guittet, S. Yoshizawa and D.
Fourmy, ”Structure of the RNA signal essential for translational frameshifting in HIV-1.” Journal of Molelcular Biology, 2005;349:1024.
Resonance 2006;179:50-8.
F. Fayon, D. Massiot, M.H. Levitt, J.J. Titman, D.H. Gregory, L. Duma,
L. Emsley, S.P. Brown. “Through-space contributions to twodimensional double-quantum J correlation NMR spectra of magicangle-spinning solids,” Journal of Chemical Physics
2005;122:194313.
P. Aliprandi, C. Sizun, J. Perez, F. Mareuil, S. Caputo, J-L. Leroy, B.
Odaert, S. Laalami, M. Uzan and F. Bontems, "S1 ribosomal protein
functions in translation initiation and ribonuclease RegB activation are
mediated by similar RNA-protein interactions" Journal of Biological
Chemistry 2008; 283:13289.
F. Fayon, G. Le Saout, L. Emsley, D. Massiot. “Through-Bond
Phosphorus-Phosphorus Connectivities in Crystalline and Disordered
Phosphates by Solid-State NMR,” Chemical Communications
2002;1702-3
D. Stratmann, C. van Heijenoort and E. Guittet, "NOEnet-Use of NOE
networks for NMR resonance assignment of proteins with known 3D
structure" Bioinformatics 2009; 11:474.
Lille/Orléans
Q. Wang, B. Hu, F. Fayon, J. Trébosc, C. Legein, O. Lafon, F. Deng,
J.P. Amoureux, "Double-quantum 19F-19F dipolar recoupling at ultrafast magic angle spinning NMR: application to the assignment of 19F
NMR spectra of inorganic fluorides"; Phys. Chem. Chem. Phys 2009;
DOI: 10.1039/b914468d.
Lille
I. Landrieu, M. da Costa, L. De Veylder, F. Dewitte, K. Vandepoele, S.
Hassan, J.M. Wieruszeski, F. Corellou, J.D. Faure, M. Van Montagu,
D. Inze, G. Lippens, “NMR structure of a small CDC25 dual-specificity
tyrosine-phosphatase isoform in Arabidopsis thaliana.” Proceedings of
the National Academy of Sciences of the United States of America
2004;101:16391.
B. Hu, J.P. Amoureux, J. Trebosc, M. Deschamps, G. Tricot, “Solidstate NMR covariance of HOMCOR spectra,” Journal of Chemical
Physics 2008; 128: 134502.
J.P. Amoureux, J. Trebosc, J.W. Wiench, D. Massiot, M. Pruski.
“Measurement of J Couplings between Spin-½ and Quadrupolar Nuclei by Frequency Selective Solid State NMR,” Solid State NMR
2005:27;228-32.
G. Tricot, L. Delevoye, G. Palavit, L. Montagne, “Phase identification
and quantification in a devitrified glass using homo- and heteronuclear
solid state NMR.” Chemical Communications 2005;5289-91.
A. Sillen, J.M. Wieruszeski, A. Ben Younes, I. Landrieu et G. Lippens,
“HRMAS NMR characterization of the Paired Helical Fragments of the
neuronal Tau protein.” Journal of the American Chemical Society
2005;127:10138-9.
D. Massiot, F. Fayon, B. Alonso, J. Trebosc, J.P. Amoureux. “Chemical
bonding differences evidenced from J coupling in solid state NMR
experiments involving quadrupolar nuclei,” Journal of Magnetic Resonance 2003;164:165-70.
I. Landrieu, L. Lacosse, A. Leroy, J.M. Wieruszeski, X. Trivelli, A.
Sillen, N. Sibille ,H. Schwalbe, K. Saxena, T. Langer, G. Lippens,
“NMR analysis of a Tau phosphorylation pattern” Journal of the
American Chemical Society 2006; 128: 3575.
Lyon/Grenoble
J. Sein, N. Giraud, M. Blackledge and L. Emsley, “The Role of 15N
CSA and CSA/Dipole Cross Correlation in 15N Relaxation in Solid
Proteins,” J. Magn. Reson. 2007; 186: 26.
Z.H. Gan, J.P. Amoureux, J. Trebosc, “Proton-detected N-14 MAS
NMR using homonuclear decoupled rotary resonance”
Chemical Physics Letters 2007; 435: 163.
N. Giraud, J. Sein, G. Pintacuda, A. Böckmann, A. Lesage, M. Blackledge and L. Emsley, “Observation of Heteronuclear Overhauser Effects Confirms the 15N-1H Dipolar Relaxation Mechanism in a Crystalline Protein,” J. Am. Chem. Soc. 2006; 128: 12398.
Orléans
N. Giraud, M. Blackledge, M. Goldman, A. Bockmann, A. Lesage, F.
Penin and L. Emsley. "Quantitative analysis of backbone dynamics in
a crystalline protein from nitrogen-15 spin-lattice relaxation." Journal
of the American Chemical Society 2005;127:18190.
S.Josse, C.Faucheux, A.Soueidan, G.Grimandi, D.Massiot, B.Alonso,
P.Janvier, S.Laïb, O.Gauthier, G.Daculsi, J.Guicheux, B.Bujoli,
J.-M.Bouler, “Chemically Modified Calcium Phosphates as Novel Materials for Bisphosphonate Delivery.” Advanced Materials
2004;16:1423-27.
N. Giraud, A. Bockmann, A. Lesage, F. Penin, M. Blackledge and L.
Emsley. "Site-specific backbone dynamics from a crystalline protein
by solid-state NMR spectroscopy." Journal of the American Chemical
Society 2004;126:11422.
M. Deschamps, F. Fayon, V. Montouillout, D. Massiot, “Through-bond
homonuclear correlation experiments in Solid-state NMR applied to
quadrupolar nuclei in Al-O-P-O-Al chains.” Chemical Communications
2006:1924-5.
M. Juy, F. Penin, A. Favier, A. Galinier, R. Montserret, R. Haser, J.
Deutscher and A. Bockmann. "Dimerization of Crh by reversible 3D
domain swapping induces structural adjustments to its monomeric
homologue Hpr." Journal of Molecular Biology 2003;332:767.
C. Martineau, F. Fayon, C. Legein, J.Y. Buzaré, G. Silly, D. Massiot,
“Accurate Heteronuclear J-Coupling Measurements in Dilute Spin
Systems using the multiple-quantum filtered J-resolved experiment,”
Chemical Communications 2007; 2720.
A. Favier, B. Brutscher, M. Blackledge, A. Galinier, J. Deutscher, F.
Penin and D. Marion. "Solution structure and dynamics of Crh, the
Bacillus subtilis catabolite repression HPr." Journal of Molecular Biology 2002;317:131.
D. Laurencin, C. Gervais, A. Wong, C. Coelho, F. Mauri, D. Massiot,
M.E. Smith, C. Bonhomme, “Implementation of high resolution 43Ca
solid state NMR spectroscopy: towards the elucidation of calcium
sites in biological materials,” Journal of the American Chemical Society 2009; 131: 13430.
F. Penin, A. Favier, R. Montserret, B. Brutscher, J. Deutscher, D. Marion and A. Galinier. "Evidence for a dimerisation state of the Bacillus
subtilis catabolite repression HPr-like protein, Crh." Journal of Molecular Microbiology and Biotechnology 2001;3:429.
G. Arrachart, G. Creff, H. Wadepohl, C. Blanc, C. Bonhomme, F. Babonneau, B. Alonso, J.L. Bantignies, C. Carcel, J.J.E. Moreau, P.
Dieudonné, J.L. Sauvajol, D. Massiot, M. Wong Chi Man, “Nanostructuring of hybrid silicas through self-recognition process,” Chemistry, A
European Journal 2009; 15: 5002.
A. Lesage, F. Penin, C. Geourjon, D. Marion and M. vanderRest.
"Trimeric assembly and three-dimensional structure model of the
FACIT collagen COL1-NC1 junction from CD and NMR analysis."
Biochemistry 1996;35:9647.
References to Collaborative Papers Between the Sites.
For further information, contact
Lyon: [email protected]
Orléans: [email protected]
Gif-sur-Yvette: [email protected]
Grenoble: [email protected]
Lille: [email protected]
Bordeaux: [email protected]
Orléans/Lyon
M. Deschamps, D. Massiot, G. Kervern, G. Pintacuda, L. Emsley and
P.J. Grandinetti, “Superadiabaticity in Magnetic Resonance,” J. Chem.
Phys. 2008;127: 204110.
F. Fayon, C.Roiland, L.Emsley, D.Massiot. “Triple-quantum correlation
NMR experiments in solids using J-couplings,” Journal of Magnetic
8