Stabilization of unusual structures in peptides using alpha,beta-dehydrophenylalanine: crystal and solution structures of Boc-Pro-DeltaPhe-Val-DeltaPhe-Ala-OMe and Boc-Pro-DeltaPhe-Gly-DeltaPhe-Ala-OMe.
The structures of two dehydropentapeptides, Boc-Pro-DeltaPhe-Val-DeltaPhe-Ala-OMe (I) and Boc-Pro-DeltaPhe-Gly-DeltaPhe-Ala-OMe (II) (Boc: t-butoxycarbonyl), have been determined by nuclear magnetic resonance (NMR), circular dichroism (CD), and X-ray crystallographic studies. The peptide I assumes a S-shaped flat beta-bend structure, characterized by two partially overlapping type II beta-bends and absence of a second 1 <-- 4 (N4--H . . . O1') intramolecular hydrogen bond. This is in contrast to the generally observed 3(10)-helical conformation in peptides with DeltaPhe at alternate positions. This report describes the novel conformation assumed by peptide I and compares it with that of the conserved tip of the V3 loop of the HIV-1 envelope glycoprotein gp120 (sequence, G:P319 to F:P324, PDB code 1ACY). The tip of the V3 loop also assumes a S-shaped conformation with Arg:P322, making an intramolecular side-chain-backbone interaction with the carbonyl oxygen of Gly:P319. Interestingly, in peptide I, C(gamma)HVal(3) makes a similar side-chain-backbone C--H . . . O hydrogen bond with the carbonyl oxygen of the Boc group. The observed overall similarity indicates the possible use of the peptide as a viral antagonist or synthetic antigen. Peptide II adopts a unique turn followed by a 3(10)-helix. Both peptides I and II are classical examples of stabilization of unusual structures in oligopeptides.
Mathur
Puniti
P
Department of NMR, All India Institute of Medical Sciences, New Delhi.
Ramagopal
U A
UA
Ramakumar
S
S
Jagannathan
N R
NR
Chauhan
V S
VS
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D002942:Circular Dichroism; D003460:Crystallization; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000032:analysis* / Q000737:chemistry; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012996:Solutions
D000596:Amino Acids; D009842:Oligopeptides; D012996:Solutions; D010649:Phenylalanine; C018632:phenyldehydroalanine