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C Isernia

Publications and source records attributed to C Isernia.

22 records · Page 2Linked to original sources
PubMedDate not supplied

Conformational behaviour of a cyclolinopeptide A analogue: two-dimensional NMR study of cyclo(Pro1-Pro-Phe-Phe-Ac6c-Ile-ala-Val8).

The cyclic octapeptide cyclo[-Pro1-Pro-Phe-Phe-Ac6c-Ile-ala-Val8-] [C8-Ac6c], containing the Pro1-Pro-Phe-Phe sequence, followed by a bulky helicogenic C alpha,alpha-dialkylated glycine residue Ac6c [1-aminocyclohexane-1-carboxylic acid), and a D-Ala residue at position 7 has been synthesized. This cyclic peptide is a deletion analogue of the naturally occurring cyclic nonapeptide cyclolinopeptide A (CLA). It has been designed with the aim of studying the role that the Ac6c and D-Ala residues play on the conformational behaviour of the whole molecule and their influence on the conformation of the Pro1-Pro-Phe-Phe sequence when compared with cyclolinopeptide A. C8-Ac6c has been investigated in chloroform and acetonitrile solutions by 2D NMR techniques. Only one set of sharp signals is observed in both solvents. This evidence strongly supports the hypothesis that only one conformational state exists in the chosen solvents. The interpretation of the experimental data points to the existence for C8-Ac6c of a very rigid structure stabilized by intramolecular hydrogen bonds. The measured NOE effects allow the calculation of internuclear distances, which have been used as restraints in molecular dynamic calculations. The proposed conformation of the molecule shows that the Pro-Pro-Phe segment retains the conformation observed in natural CLA both in solution and in the solid state and that the Ac6c residue indeed reinforces the ring rigidity not permitting the formation of any appropriate cavity in which inorganic cations could be complexed.

Amino Acid Sequence↗
PubMedDate not supplied

Elucidation of the structure of constrained bicyclopeptides in solution by two-dimensional cross-relaxation spectroscopy: amatoxin analogues.

The evaluation of peptide structures in solution is made feasible by the combined use of two-dimensional NMR in the laboratory (NOESY) and rotating frames (ROESY), and by the use of molecular dynamics calculations. The present paper describes how both the NMR method and molecular dynamics calculations were applied to very rigid synthetic bicycle peptides that are analogues of natural amatoxins. The NMR theory, which allows the estimate of interatomic distances between interacting nuclei, is briefly discussed. The experimental data were compared with those of known solid-state structures. Three amatoxin analogues have been examined. Of these, one is biologically active (S-deoxo gamma[R] OH-Ile3-amaninamide) and its structure in the solid state has recently been worked out. The second and third analogues (S-dexo-Ile3-Ala5-amaninamide and S-deoxo-D-Ile3-amaninamide, respectively) are inactive and their solid-state structures are unknown. The data presented confirm the authors previous hypothesis that lack of biological activity of S-deoxo-Ile3-Ala5-amaninamide is due to the masking of the tryptophan ring by the methyl group of L-Ala and not to massive conformational changes of the analogue.

Amanitins↗