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M Genest

Publications and source records attributed to M Genest.

45 records · Page 3Linked to original sources

Empirical calculations on cyclic dipeptides. Conformations of aspartic acid, glutamic acid and histidine residues.

Empirical conformational energy calculations were carried out for the dipeptides cyclo-(L-Asp-L-His) and cyclo-(L-Glu-L-His). The side chain conformations have been studied for various DKP ring structures, demonstrating that distortions can modify the stability of some conformations by favouring peptide backbone-side chain or side chain-side chain interactions. The carboxylic side chain of Asp and Glu residues can induce specific interactions with the imidazole ring or the peptide bond of the DKP ring which are not found for Ser or Thr. The necessity of including solute--solvent interactions to account for a more realistic conformational behaviour is discussed.

Dipeptides↗

Empirical calculations on cyclic dipeptides. Conformations of serine, threonine and histidine residues.

Empirical conformational energy calculations were carried out for the dipeptides cyclo-(L-Ser-L-His) and cyclo-(L-Thr-L-His). Various DKP structures have been investigated to study side chain conformations through the DKP ring deformations, and prevalent conformers of monosubstituted and disubstituted dipeptides are discussed. The most stable conformations occur when both side chains are folded over a planar DKP ring, the imidazole ring being in the epsilon-tautomeric form. Theoretical results are consistent with those obtained from n.m.r. and crystallographic studies.

Histidine↗

Lipopeptides with improved properties: structure by NMR, purification by HPLC and structure-activity relationships of new isoleucyl-rich surfactins.

The biosynthesis of bacterial isoleucyl-rich surfactins was controlled by supplementation of L-isoleucine to the culture medium. Two new variants, the [Ile4,7]- and [Ile2,4,7]surfactins, were thus produced by Bacillus subtilis and their separation was achieved by reverse-phase HPLC. Amino acids of the heptapeptide moiety were analysed by chemical methods, and the lipid moiety was identified by beta-hydroxy anteiso pentadecanoic acid by combined GC/MS. Sequences were established on the basis of two-dimensional NMR data. Because conformational parameters issuing from NMR spectra suggested that the cyclic backbone fold was globally conserved in the new variants, structure-activity relationships were discussed in details on the basis of the three-dimensional model of surfactin in solution. Indeed, both variants have increased surface properties compared with that of surfactin, and this improvement is assigned to an increase of the hydrophobicity of the apolar domain favouring micellization. Furthermore, the additional Leu-to-Ile substitution at position 2 in the [Ile2,4,7]surfactin leads to a substantial increase of its affinity for calcium, when compared with that of [Ile4,7]surfactin or surfactin. This effect is assigned, from the model, to an increase in the accessibility of the acidic side chains constituting the calcium binding site. Thus, the propensities of such active lipopeptides for both hydrophobic and electrostatic interactions were improved, further substantiating that they can be rationally designed.

Amino Acids↗

Progress in multidimensional NMR investigations of peptide and protein 3-D structures in solution. From structure to functional aspects.

2-D and 3-D NMR techniques were used to investigate the conformations in solution of several peptides and proteins for which crystalline structures are not available yet. Insect defensin A is a small (40 aa) antibiotic protein exhibiting a characteristic 'loop-helix-beta-sheet' structure. A striking analogy was found with charybdotoxin, a scorpion toxin in which a CSH (cysteine stabilized alpha-helix) motif is also present. Wheat phospholipid transfer protein (PLTP) (90 aa) has a 3-D structure resulting from the packing of four helices and of a C-terminal less well-defined fragment. Preliminary results show that PLTP forms a complex with lyso-PC and that such an interaction results in a conformational change affecting principally the C-terminal half of the protein. A last example is given with surfactin, a lipopeptide biosurfactant from bacterial origin. Its protonated form shows a very compact structure in which the two acidic residues located on the top of a 'horse saddle' topology face each other, whereas the ionized form could adopt a more extended conformation. A common property of these compounds is their capacity to interact with lipids. The present structural data open the way for a further establishment of structure-activity relationships.

Amino Acid Sequence↗

[Cage failure following replacement of the third lumbar vertebral body in Hodgkin's disease].

AIM: We present a case report and the histological analysis of cage failure following vertebral body replacement in Hodgkin's disease. METHOD: In a 35-year-old patient with a single metastasis of Hodgkin's disease replacement of the third lumbar vertebral body (Harms-titanium-mesh-cage, DePuy Acromed, completely filled with autogenous spongiosa from the iliac crest) was performed. 51 months postoperatively, the patient presented with acute back pain without trauma. The X-ray showed a collapse of the Harms-titanium-mesh-cage. The cage fragments had caused ventral dislocation of the main blood vessels and dura compression without neurological deficits. After the replacement of the failed Harms-cage (Synex, Synthes) histological analysis (light microscope, non-decalcified horizontal cuts, thickness of 150-200 microm, Giemsa und van Gieson staining) was done. RESULT: The histology showed a remodelling of new bone in the area of the endplates without contact to the cage wall. In the region of the cage corpus, bony necrosis and connective tissue rich in cells was found. CONCLUSION: Bridging fusion in vertebral body replacement cages is not proven. As a result cage failure may occur. Therefore, in tumour patients with high live expectancy, Palacos filling of the cages should be discussed.

Adult↗

Preparation for childbirth--evidence for efficacy. A review.

Recent research on pain and psychoprophylaxis in relation to preparation for childbirth are examined. The various findings seem to lead to the value of childbirth preparation classes in lowering anxiety levels and altering patients' assessments of their impending labors. These changes in patients' appraisals are reflected in the experience of childbirth: in lowered perceptions of pain and more positive feelings about the birth.

Female↗