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. [10.1002/1099-0690(200007)2000:14<2563::AID-EJOC2563>3.0.CO;2-3]
Conformational analysis of azabicycloalkane amino acid scaffolds as reverse-turn inducer dipeptide mimics
L. BelvisiPrimo
;A. BernardiSecondo
;L. Manzoni;D. PotenzaPenultimo
;C. ScolasticoUltimo
2000
Abstract
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.Pubblicazioni consigliate
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