Simulated annealing study of the pentacyclo-undecane cage amino acid tripeptides of the type [Ac-X-Y-Z-NHMe]

摘要

The conformational preferences of the four peptide analogues [A] = Ac-Ala-Ala-Ala-NHMe, [13] = Ac-Cage-Cage-Cage-NHme, [C] = Ac-AlaCage-Ala-NHMe and [D] = Ac-Ala-Pro-Ala-NHMe were carried out using iterative simulated annealing (SA) at the molecular mechanics level using the amber force field. The overall conformational search indicates that the pentacyclo-undecane (PCU) Cage imposes a greater restriction on the conformational freedom of the tripeptide in comparison with proline. The first 20 low energy conformations were also analyzed for beta-turns or reverse-turn characteristics. This theoretical study revealed that [D] proved to be the most effective P-turn promoter (35%) within the peptide series [A]-[D]. The pentacyclo-undecane amino acid exhibit promising beta-turn characteristics in cases [B] and [C] (15%). In most cases for [A][D], the low energy structures are bent although none of the unique structures for [A] satisfy all three criteria for beta-tums. The peptide sequences [B]-[D] can be classified as canonical reverse beta-type I, II or III turns. (c) 2005 Elsevier B.V. All rights reserved.