In an effort to design structural mimics of protein and peptide reverse- turns, the conformations of 5,5-, 6,5-, and 7,5-fused 1-aza-2- oxobicycloalkane amino acids have been evaluated. The conformational preferences of these proline-derived bicyclic lactams have been studied by Monte Carlo molecular mechanics searches, and the reverse-turn inducing properties of the calculated structures have been quantitatively assessed using various geometrical parameters. All of the four possible diastereoisomers arising from two of the three stereogenic centres [C3 and bridgehead carbon atom; Pro Cα is (S) in all compounds] have been considered for each bicyclic scaffold. These studies have revealed that the (3S)-Pro Cα(S) configuration is an effective turn-inducer, although the torsion angles of the backbone do not always mimic those of classical β-turns. A dependence of the turn-inducing ability on lactam ring size and bridgehead stereochemistry has also been found. Reverse-turn mimetic bicyclic lactams have been shown to exhibit a tendency to form an inverse γ-turn or a type II' β-turn. Experimental H-NMR and FT-IR spectroscopic data of model compounds in chloroform solutions have complemented our computer modelling studies and have confirmed our conclusions.
Conformational analysis of azabicycloalkane amino acid scaffolds as reverse-turn inducer dipeptide mimics / L. Belvisi, A. Bernardi, L. Manzoni, D. Potenza, C. Scolastico. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1434-193X. - :14(2000), pp. 2563-2569.
|Titolo:||Conformational analysis of azabicycloalkane amino acid scaffolds as reverse-turn inducer dipeptide mimics|
BELVISI, LAURA (Primo)
BERNARDI, ANNA (Secondo)
POTENZA, DONATELLA (Penultimo)
SCOLASTICO, CARLO (Ultimo)
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Data di pubblicazione:||2000|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/1099-0690(200007)2000:14<2563::AID-EJOC2563>3.0.CO;2-3|
|Appare nelle tipologie:||01 - Articolo su periodico|