Theoretical and experimental studies on alpha/epsilon-hybrid peptides: design of a 14/12-helix from peptides with alternating (S)-C-linked carbo-epsilon-amino acid [(S)-epsilon-Caa((x))] and L-ala.
An (S)-C-linked carbo-epsilon-amino acid [(S)-epsilon-Caa((x))] was prepared from the known (S)-delta-Caa. This monomer was utilized together with l-Ala to give novel alpha/epsilon-hybrid peptides in 1:1 alternation. Conformational analysis on penta- and hexapeptides by NMR (in CDCl(3)), CD, and MD studies led to the identification of robust 14/12-mixed helices. This is in agreement with the data from a theoretical conformational analysis on the basis of ab initio MO theory providing a complete overview on all formally possible hydrogen-bonded helix patterns of alpha/epsilon-hybrid peptides with 1:1 backbone alternation. The "new motif" of a mixed 14/12-helix was predicted as most stable in vacuum. Obviously, the formation of ordered secondary structures is also possible in peptide foldamers with amino acid constituents of considerable backbone lengths. Thus, alpha/epsilon-hybrid peptides expand the domain of foldamers and allow the introduction of desired functionalities via the alpha-amino acid constituents.
Sharma
Gangavaram V M
GV
Organic Chemistry Division III, Indian Institute of Chemical Technology (CSIR), Hyderabad 500 607, India. esmvee@iict.res.in
Babu
Bommagani Shoban
BS
Chatterjee
Deepak
D
Ramakrishna
Kallaganti V S
KV
Kunwar
Ajit C
AC
Schramm
Peter
P
Hofmann
Hans-Jörg
HJ
D000409:Alanine / Q000737:chemistry*; D020816:Amino Acid Motifs; D000596:Amino Acids / Q000737:chemistry*; D002625:Chemistry, Organic / Q000379:methods*; D002942:Circular Dichroism; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000737:chemistry; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary
D000596:Amino Acids; D010455:Peptides; D000409:Alanine; D000432:Methanol