Design of a "new motif" with beta-amino acids and alpha-aminoxy acids: Synthesis of hybrid peptides with 12/10-helix

作者：Sharma Gangavaram V A^*; Manohar Vennampalli; Dutta Samit K; Subash Velaparthi; Kunwar Ajit C

来源：Journal of Organic Chemistry, 2008, 73(10): 3689-3698.

DOI：10.1021/jo702242q

Hybrid peptides are prepared from a C-linked carbo-beta-amino acid ester (R-beta-Caa) and an a.-aminoxy acid (R-Ama) derived from S-lactic acid. Extensive NMR (in CDCl(3) solution), CD, and MD studies on the tetra- and hexapeptides led to identification of robust 12/10-mixed helices. The dipeptide repeat having an R-beta-Caa and an R-Ama thus provides a "new motif" to realize a 12/10-mixed helix, for the first time, in oligomers containing R-Ama. To understand the impact of side chains in the mixed helix formation, R-beta-Caa/Ama (with no substitution in Ama) and S-beta-hAla/R-Ama oligomers were investigated. NMR studies revealed the existence of 12/10-helices in these hybrid peptides, and the side chains of monomers were found to have a profound influence on their stabilities. These observations imply that the propensity of beta-amino acid to prefer a mixed 12/10-helix governs the structural behavior in these peptides. The structural consequences of the lone-pair repulsion between nitrogen and oxygen atoms result in a new and interesting structural motif which behaves like "pseudo" beta(3),beta(2)-peptides in generating 12/10-mixed helices.

• 出版日期2008-5-16