Context
$alpha,beta$hybrid peptides:a polypeptide helix with a central segment containing two consecutive $beta$-amino acid residues
Title:
$alpha,beta$hybrid peptides:a polypeptide helix with a central segment containing two consecutive $beta$-amino acid residues
Archive:
Eprints@iisc
Author(s):
Roy, Rituparna S
Karle, Isabella L
Raghothama, S
Balaram, P
Karle, Isabella L
Raghothama, S
Balaram, P
Date:
2004-11-01
Abstract:
Conformational studies on the synthetic 11-aa peptide t-butoxycarbonyl
(Boc)-Val-Ala-Phe-$alpha$-aminoisobutyric acid (Aib)-(R)-$beta^3$- homovaline ($beta$Val)-(S)-$beta^3$-homophenylalanine ($beta$Phe)-Aib-Val-Ala- Phe-Aib-methyl ester (OMe) (peptide 1; $beta$Val and $beta$Phe are $beta$amino acids generated by homologation of the corresponding L-residues) establish that insertion of two consecutive $beta$ residues into a polypeptide helix can be accomplished without significant structural distortion. Crystal-structure analysis reveals a continuous
helical conformation encompassing the segment of residues 2?10 of peptide 1. At the site of insertion of the $betabeta$ segment, helical hydrogen-bonded rings are expanded. A $C_1_5$ hydrogen bond for the $alphabetabeta$segment and two $C_1_4$ hydrogen bonds for the $alphaalphabeta$or $betaalphaalpha$ segments have been characterized. The following conformational angles were determined from the crystal structure for the $beta$ residues: $beta$ Val-5 ($phi = -126 ^o $,$theta = 76 ^o $ , and $psi = -124$) and $beta$Phe-6 ($phi = - 88^o,$ $theta = 80^o,$ and $psi = - 118$). The N terminus of the peptide is partially unfolded in crystals. The 500-MHz $^1H-NMR$ studies
establish a continuous helix over the entire length of the peptide in $CDCl_3$ solution, as evidenced by diagnostic nuclear Overhauser effects. The presence of seven intramolecular hydrogen bonds is also established by using solvent dependence of NH chemical shifts.
(Boc)-Val-Ala-Phe-$alpha$-aminoisobutyric acid (Aib)-(R)-$beta^3$- homovaline ($beta$Val)-(S)-$beta^3$-homophenylalanine ($beta$Phe)-Aib-Val-Ala- Phe-Aib-methyl ester (OMe) (peptide 1; $beta$Val and $beta$Phe are $beta$amino acids generated by homologation of the corresponding L-residues) establish that insertion of two consecutive $beta$ residues into a polypeptide helix can be accomplished without significant structural distortion. Crystal-structure analysis reveals a continuous
helical conformation encompassing the segment of residues 2?10 of peptide 1. At the site of insertion of the $betabeta$ segment, helical hydrogen-bonded rings are expanded. A $C_1_5$ hydrogen bond for the $alphabetabeta$segment and two $C_1_4$ hydrogen bonds for the $alphaalphabeta$or $betaalphaalpha$ segments have been characterized. The following conformational angles were determined from the crystal structure for the $beta$ residues: $beta$ Val-5 ($phi = -126 ^o $,$theta = 76 ^o $ , and $psi = -124$) and $beta$Phe-6 ($phi = - 88^o,$ $theta = 80^o,$ and $psi = - 118$). The N terminus of the peptide is partially unfolded in crystals. The 500-MHz $^1H-NMR$ studies
establish a continuous helix over the entire length of the peptide in $CDCl_3$ solution, as evidenced by diagnostic nuclear Overhauser effects. The presence of seven intramolecular hydrogen bonds is also established by using solvent dependence of NH chemical shifts.
Index terms:
Discipline(s):
Molecular Biophysics Unit
Subject(s):
Method/Approach:
Coverage:
Publisher:
Contributors:
Source:
Language:
Relation:
Type:
Journal Article
Format:
pdf http://eprints.iisc.ernet.in/secure/00005913/01/sl.no.53-pdf.pdf
Copyright Information:
Browse Archive