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M Marraud

Publications and source records attributed to M Marraud.

At least 19 recordsLinked to original sources
PubMed1992

Hydration of the Gly2 and Gly3 peptide oxygens of [Leu5]-enkephalin in aqueous solution as revealed by the combined use of 17O-NMR and Fourier-transform infrared spectroscopy.

Solvent-induced and temperature-induced 17O chemical shifts of [17O-Gly2, Leu5]-enkephalin and [17O-Gly3, Leu5]-enkephalin and solvent-induced spectral modifications of the amide-I' stretching vibrations of [1-13C-Gly2, Leu5]-enkephalin and [1-13C-Gly2, Leu5]-enkephalin are reported and correlated with the spectroscopic characteristics of model amides. It is demonstrated that both Gly2 and Gly3 peptide oxygens are motionally equivalent and form solvation species which are essentially monohydrated in aqueous solution, contrary to several simple amides and model peptides in which water largely forms dihydrates. It is shown that the combined use of 17O-NMR and Fourier transform infrared is a unique methodology for studying the hydration state of specific peptide oxygens in peptide hormones.

Deuterium↗
PubMed1992

17O NMR and FT-IR study of the ionization state of peptides in aprotic solvents. Application to Leu-enkephalin.

The ionization state of Leu-enkephalin in DMSO and MeCN/DMSO (4/1) solution was studied by the combined use of 17O NMR and FT-IR spectroscopy. After lyophilization of an aqueous solution at nearly neutral pH, Leu-enkephalin essentially exists in the uncharged state in MeCN/DMSO (4/1) solution. In pure DMSO, only 40% of the Leu-enkephalin molecules are in the zwitterionic state under the same conditions.

Amino Acid Sequence↗
PubMed1992

Structure of tBuCO-Gly-Gly psi [CH2-N+H2]NHEt.BPh4-.

N-(tert-Butylcarbonylglycylaminoethyl)-N-(ethyl)ammonium tetraphenylborate, C11H24N3O+2.C24H20B-, Mr = 549.57, triclinic, P-1, a = 11.567 (2), b = 11.922 (2), c = 14.484 (3) A, alpha = 70.99 (2), beta = 74.83 (2), gamma = 59.33 (1) degrees, V = 1613.1 A3, Z = 2, D chi = 1.13 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 4.69 cm-1, mu Rmax much less than 1, F(000) = 592, T = 293 K, R = 0.058 for 3491 observed reflections. This pseudopeptide is folded by a short N(+)-H ... O = C hydrogen bond (N3 ... O1 = 2.81 A) which closes a ten-membered ring. This results in a beta-turn structure that can be classified as type II on the basis of the conformational angles for the N-terminal glycine. The conformational angles phi 1, psi 1, phi 2 and psi 2 are -53.4 (6), 139.7 (4), 91.5 (5) and -62.6 (6) degrees respectively.

Amino Acid Sequence↗
PubMed1992

Structure of tBuCO-Val psi [NH-CO]NHtBu.

N-Isobutylidenedipivalamide, C14H28N2O2, Mr = 256.39, orthorhombic, P2(1)2(1)2(1), a = 16.656 (2), b = 9.751 (2), c = 10.583 (2) A, V = 1718.8 A3, Z = 4, D chi = 0.99 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 4.56 cm-1, mu Rmax much less than 1, F(000) = 568, T = 293 K, R = 0.081 for 887 observed reflections. The geometrical parameters of this retro-peptide molecule are quite similar to the standard values for peptides. Conformational angles are phi = -101 (1), phi' = 99 (1) degrees.

Amino Acid Sequence↗
PubMed1992

Structure of MeCO-Gly psi [NH-CO]NHMe.

N,N'-Methylenediacetamide, C5H10N2O2, Mr = 130.15, orthorhombic, Pna2(1), a = 17.218 (1), b = 4.489 (1), c = 18.124 (1) A, V = 1400.8 A3, Z = 8, D chi = 1.23 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu Rmax much less than 1, mu = 7.19 cm-1, F(000) = 560, T = 293 K, R = 0.044 for 1318 observed reflections. This retro-peptide molecule assumes two nearly identical conformational states (A phi = 93.2, phi' = 77.0; B phi = 90.6, phi' = 79.6 degrees) with planar trans amide functions. The bond lengths and bond angles are very close to the standard dimensions of the peptide group.

Acetamides↗
PubMed1992

Structure of MeCO-psi[NH-CO]Val-NHMe.

N,N'-Dimethylisopropylmalonamide, C8H16N2O2, Mr = 172.23, orthorhombic, Pbcm, a = 4.859 (1), b = 13.523 (2), c = 15,469 (2) A, V = 1016.4 A3, Z = 4, Dx = 1.12 g cm-3, lambda(Cu K alpha) = 1.5418 A, microRmax much less than 1, mu = 5.88 cm-1, F(000) = 376, T = 293 K, R = 0.060 for 665 observed reflections. Dimensions of this retropeptide molecule are quite similar to the standard values for peptides. The C alpha and C beta atoms are in a mirror (z = 1/4), so conformational angles are psi' = -psi = -110.4 degrees (2).

Amino Acid Sequence↗
PubMed1992

Structural variations in the crystal structures of two homologous DL-Leu and delta-Leu containing peptides.

The similar conformations and interaction modes of Ac-DL-Leu-NMe2 and Ac-delta-Leu-NMe2 molecules in the solid state allow the comparison of their geometrical parameters. The most evident variations are essentially restricted to the alpha, beta-unsaturated side-chain which adopts the Z-disposition. The dimensions of the peptide backbone are much less sensitive to alpha, beta-unsaturation, with a small shortening by 0.04 A and 0.02 A of the N--C alpha and C alpha--C' bonds, respectively, and an increase by 6 degrees of the N--C alpha--C' bond angle. The ethylenic and amide groups in the delta-Leu derivative are far from coplanarity, and a significant electronic conjugation of the pi-orbital is likely to be rejected.

Crystallization↗
PubMed1991

Electron distributions in peptides and related molecules. 1. An experimental and theoretical study of N-acetyl-L-tryptophan methylamide.

The thermal vibrations and electron density of N-Ac-L-Trp-NHMe have been analyzed using single-crystal X-ray diffraction data measured at 103 K with Mo K alpha radiation to a resolution corresponding to (sin theta max)/ lambda = 1.17 A-1. Measurements of 10,527 reflections gave 4913 unique data [R(int)(magnitude of F2) = 0.019] of which 2641 had I greater than 3 sigma (I). A multipolar atomic density model was fitted [R(magnitude of F) = 0.028] in order to calculate phases for the crystal structure factors and map the valence-electron distribution. The phase problem for determining deformation densities by Fourier synthesis for noncentrosymmetric crystals is discussed. The experimental density agrees well with the theoretical density from an ab initio SCF molecular wave function calculated at the crystallographic molecular geometry with a split-valence basis set. Both the experimental and theoretical analyses confirm that the electron distribution is the same in the two different peptide groups in the molecule. Crystal data: C14H17N3O2, Mr = 259.31, orthorhombic, P2(1)2(1)2(1), Z = 4, F(000) = 522 e from 295 to 103 K; at 295 K, a = 8.152(2), b = 11.170 (2), c = 15.068 (3) A, V = 1372 A3, Dx = 1.26 mg mm-3; at 103 K, a = 8.209 (3), b = 11.016 (2), c = 14.760 (4) A, V = 1135 A3, Dx = 1.29 mg mm-3, mu = 0.083 mm-1 for lambda = 0.7107 A.

Chemical Phenomena↗
PubMed1991

Two-dimensional 1H-NMR study of antigen-antibody interactions: binding of synthetic decapeptides to an anti-acetylcholine receptor monoclonal antibody.

Two-dimensional NMR experiments [correlated spectroscopy (COSY) and two-dimensional transferred nuclear Overhauser enhancement spectroscopy (TR-NOESY)] have been applied to study the interactions of a monoclonal antibody (mAb) directed to the main immunogenic region (MIR) of the acetylcholine receptor (AChR), and four synthetic decapeptides from the MIR. The decapeptides were the Torpedo AChR alpha 67-76 fragment (W67-N68-P69-A70-D71-Y72-G73-+ ++G74-I75-K76) and its three [A69], [A73], and [A76] analogues. The results led to the following conclusions: (1) the magnitude of the TR-NOE cross peaks does not depend only on the structuration of the peptide in the bound state, but also on restrictions of the mobility, i.e., on the correlation time tau c, which can be different for every residue; (2) the binding capacity of the synthetic peptides to mAbs measured by radioimmunoassay is directly correlated to the NOE magnitude; and (3) the combined interpretation of the COSY and TR-NOESY experiments gives a qualitative information about the nature and the overall conformation of the sequence which is in contact with the mAb binding site.

Amino Acid Sequence↗
PubMed1991

X-ray conformational study of hydrazino peptide analogues.

We have solved the crystal structures of nine pseudo-peptide analogues deriving from the hydrazino analogue of glycine or valine (N beta H2-N alpha H-C alpha HR-CO2H, R = H or iPr) or proline (N beta H2-N alpha-C alpha H-CO2H) and containing the hydrazide (CO-N beta H-N alpha less than) or N beta-Z-aminoamide [formula; see text] [CO-N alpha(N beta HZ)] peptidomimetic link. This study gives access to the average geometry of these two links, to their inter- and intramolecular interaction modes, and to their influence on the conformational properties of the molecules.

Amino Acid Sequence↗
PubMed1991

The main immunogenic region (MIR) of the nicotinic acetylcholine receptor and the anti-MIR antibodies.

Myasthenia gravis (MG) is caused by autoantibodies against the nicotinic acetylcholine receptor (AChR) of the neuromuscular junction. The anti-AChR antibodies are heterogeneous. However, a small region on the extracellular part of the AChR alpha subunit, called the main immunogenic region (MIR), seems to be the major target of the anti-AChR antibodies, but not of the specific T-cells, in experimental animals and possibly in MG patients. The major loop of the overlapping epitopes for all testable anti-MIR monoclonal antibodies (MAbs) was localized within residues 67-76 (WNPADYGGIK for Torpedo and WNPDDYGGVK for human AChR) of the alpha subunit. The N-terminal half of alpha 67-76 is the most critical, Asn68 and Asp71 being indispensable for binding. Yet anti-MIR antibodies are functionally and structurally quite heterogeneous. Anti-MIR MAbs do not affect channel gating, but they are very potent in mediating acceleration of AChR degradation (antigenic modulation) in cell cultures and in transferring experimental MG in animals. Fab fragments of anti-MIR MAbs bound to the AChR prevent the majority of the MG patients' antibodies from binding to and causing loss of the AChR. Whether this inhibition means that most MG antibodies bind on the same small region or is a result of broad steric/allosteric effects is under current investigation.

Adult↗
PubMed1991

Changes in the c.d. spectra of calf thymus DNA induced by sequential polypeptides in aqueous solutions. Part I.

Interactions of calf thymus DNA with sequential polypeptides were studied using c.d. spectroscopy in aqueous solutions. It was found that DNA structural alterations induced by sequential polypeptides (L-Arg-X-Gly)n (where X = L-Val, Leu, Ile, Nva, Nle) are modulated by the nature of the X residue. Thus, the polypeptide (L-Arg-L-Nva-Gly)n induced the 10.2B-DNA form, whereas the polypeptides (L-Arg-L-Ile-Gly)n having one methyl group less on the X residue side chain, did not provide any significant modification to the structure of DNA. The effect of ionic strength from 0.14 M NaCl (physiological value) to zero was also analysed on the basis of the observed c.d. changes and the degree of complexation in the DNA-polypeptides was estimated.

Amino Acid Sequence↗
PubMed1991

Changes in the c.d. spectra of calf thymus DNA induced by sequential polypeptides in trifluoroethanol solutions. Part II.

Interactions between calf thymus DNA and (L-Arg-X-Gly)n sequential polypeptides (where X = L-Ala, Val, Leu, Ile, Nva, Nle) in trifluoroethanol: water (40:60) solutions in the salt range of 0.12-0.5 M NaCl, were studied using c.d. spectroscopy. It was found that DNA tertiary structure (psi form) is modulated by the nature of the polypeptides (variation of X residue). The effect of the secondary structure of polypeptides on the formation of psi-DNA was also analysed. Unordered polypeptides destabilized psi aggregates, while helical polypeptides favoured DNA tertiary structure. A loss of tertiary structure was observed in the presence of the (L-Arg-L-Val-Gly)n, which can be attributed to the ability of valine to suppress psi-type DNA.

Amino Acid Sequence↗
PubMed1991

Synthesis, crystal structure and molecular conformation of the tBuCO-D,L-Ala-delta Z-Phe-NHiPr alpha,beta-unsaturated dipeptide.

The crystal structure of the tBuCO-D,L-Ala-delta Z-Phe-NHiPr dipeptide has been solved by X-ray diffraction. The peptide crystallizes in monoclinic space group P2(1)/c with a = 13.445 (3) A, b = 35.088 (4) A, c = 14.755 (3) A, beta = 116.73 (1) degree, Z = 12 and dc = 1.151 g.cm-3. The three independent molecules per asymmetric unit accommodate a beta II-folded conformation, but only one of them contains the typical i + 3----i interaction characterizing a beta-turn. In the other two molecules, the N...O distance exceeds 3.2 A, a value generally considered the upper limit for hydrogen bonds in peptides. In solution, the beta II-turn conformation is largely predominant.

Dipeptides↗
PubMed1991

The main immunogenic region of the acetylcholine receptor. Structure and role in myasthenia gravis.

Auto-antibodies to the nicotine acetylcholine receptor (AChR) cause the disease myasthenia gravis (MG). Animals immunized with AChR or receiving anti-AChR antibodies acquire MG symptoms. The majority of the monoclonal antibodies (mAbs) raised in rats against intact AChR bind to a region on the extracellular side of the AChR's alpha-subunit, the main immunogenic region (MIR). The major loop of the overlapping epitopes for several anti-MIR mAbs has been localised between residues 67-76 of the alpha-subunit. Anti-MIR mAbs are very potent in accelerating AChR degradation (antigenic modulation) in muscle cell cultures and transferring experimental MG in animals. Fab fragments of single anti-MIR mAbs when bound to the AChR inhibit two-thirds of the MG patients' antibodies from binding and from inducing antigenic modulation of the AChR. This suggest that the majority of the human MG antibodies are also directed against the MIR. It has however to be verified by direct experiments.

Animals↗
PubMed1990

Antigenic role of single residues within the main immunogenic region of the nicotinic acetylcholine receptor.

The target of most of the autoantibodies against the acetylcholine receptor (AChR) in myasthenic sera is the main immunogenic region (MIR) on the extracellular side of the AChR alpha-subunit. Binding of anti-MIR monoclonal antibodies (mAbs) has been recently localized between residues alpha 67 and alpha 76 of Torpedo californica electric organ (WNPADYGGIK) and human muscle (WNPDDYGGVK) AChR. In order to evaluate the contribution of each residue to the antigenicity of the MIR, we synthesized peptides corresponding to residues alpha 67-76 from Torpedo and human AChRs, together with 13 peptide analogues. Nine of these analogues had one residue of the Torpedo decapeptide replaced by L-alanine, three had a structure which was intermediate between those of the Torpedo and human alpha 67-76 decapeptides, and one had D-alanine in position 73. Binding studies employing six anti-MIR mAbs and all 15 peptides revealed that some residues (Asn68 and Asp71) are indispensable for binding by all mAbs tested, whereas others are important only for binding by some mAbs. Antibody binding was mainly restricted to residues alpha 68-74, the most critical sequence being alpha 68-71. Fish electric organ and human MIR form two distinct groups of strongly overlapping epitopes. Some peptide analogues enhanced mAb binding compared with Torpedo and human peptides, suggesting that the construction of a very antigenic MIR is feasible.

Amino Acid Sequence↗