Design of a "new motif" with beta-amino acids and alpha-aminoxy acids: synthesis of hybrid peptides with 12/10-helix.
Hybrid peptides are prepared from a C-linked carbo-beta-amino acid ester (R-beta-Caa) and an alpha-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.
Sharma
Gangavaram V M
GV
D-211, Discovery Laboratory, Organic Chemistry Division III and Centre for Nuclear Magnetic Resonance, Indian Institute of Chemical Technology, Hyderabad, India. esmvee@iict.res.in
Manohar
Vennampalli
V
Dutta
Samit K
SK
Subash
Velaparthi
V
Kunwar
Ajit C
AC
D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry*; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008956:Models, Chemical; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D017433:Protein Structure, Secondary; D013237:Stereoisomerism
D000596:Amino Acids; D010455:Peptides