Data di Pubblicazione:
2001
Citazione:
Crystal-state conformation of Cα,α-dialkylated peptides containing chiral β-homo-residues / A. Romanelli, I. Garella, V. Menchise, R. Iacovino, M. Saviano, D. Montesarchio, C. Didierjean, P.D. Lello, F. Rossi, E. Benedetti. - In: JOURNAL OF PEPTIDE SCIENCE. - ISSN 1075-2617. - 7:1(2001 Jan), pp. 15-26. [10.1002/psc.278]
Abstract:
Secondary structure formation and stability are essential features in the knowledge of complex folding topology of biomolecules. To better understand the relationships between preferred conformations and functional properties of beta -homo-amino acids, the synthesis and conformational characterization by X-ray diffraction analysis of peptides containing conformationally constrained C-alpha,C-alpha-dialkylated amino acid residues, such as alpha -aminoisobutyric acid or 1-aminocyclohexane-1-carboxylic acid and a single beta -homo-amino acid, differently displaced along the peptide sequence have been carried out. The peptides investigated are: Boc-beta HLeu-(Ac(6)c)(2)-OMe, Boc-Ac(6)c-beta HLeu-(Ac(6)c)(2)-OMe and Boc-beta HVal-(Aib)(5)-OtBu, together with the C-protected beta -homo-residue HCl .H beta HVal-OMe. The results indicate that the insertion of a betaH-residue at position 1 or 2 of peptides containing strong helix-inducing, bulky C-alpha,C-alpha-disubstituted amino acid residues does not Induce any specific conformational preferences. In the crystal state, most of the NH groups of beta -homo residues of tri- and tetrapeptides are not involved in intramolecular hydrogen bonds, thus failing to achieve helical structures similar to those of peptides exclusively constituted of C-alpha,C-alpha-disubstituted amino acid residues. However, by repeating the structural motifs observed in the molecules investigated, a beta -pleated sheet secondary structure, and a new helical structure, named (14/15)-helix, were generated, corresponding to calculated minimum-energy conformations. Our findings, as well as Literature data, strongly indicate that conformations of betaH-residues, with the mu torsion angle equal to - 60 degrees, are very unlikely.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
alpha,alpha-dialkylated amino acids; beta-homo amino acids; peptide synthesis; X-ray structure; beta-pleated sheet; structural biology; biochemistry; molecular medicine; molecular biology; pharmacology; drug discovery3003 pharmaceutical science; organic chemistry
Elenco autori:
A. Romanelli, I. Garella, V. Menchise, R. Iacovino, M. Saviano, D. Montesarchio, C. Didierjean, P.D. Lello, F. Rossi, E. Benedetti
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