Peptide hairpins with strand segments containing α- and β-amino acid residues: Cross-strand aromatic interactions of facing Phe residues

Roy, Rituparna S. ; Gopi, Hosahudya N. ; Raghothama, S. ; Gilardi, Richard D. ; Karle, Isabella L. ; Balaram, Padmanabhan (2005) Peptide hairpins with strand segments containing α- and β-amino acid residues: Cross-strand aromatic interactions of facing Phe residues Biopolymers: Peptide Science, 80 (6). pp. 787-799. ISSN 0006-3525

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Official URL: http://www3.interscience.wiley.com/journal/1104952...

Related URL: http://dx.doi.org/10.1002/bip.20294

Abstract

The incporation of β-amino acid residues into the strand segments of designed β-hairpin leads to the formation of polar sheets, since in the case of β-peptide strands, all adjacent carbonyl groups point in one direction and the amide groups orient in the opposite direction. The conformational analysis of two designed peptide hairpins composed of α/β-hybrid segments are described: Boc-βLeu-βPhe-Val-D-Pro-Gly-βLeu-βPhe-Val-OMe (1) and Boc-βLeu-Phe-βVal-D-Pro-Gly-βLeu-Phe-βVal-OMe (2). A 500-MHz 1H-NMR (nuclear magnetic resonance) analysis in methanol supports a significant population of hairpin conformations in both peptides. Diagnostic nuclear Overhauser effects (NOEs) are observed in both cases. X-ray diffraction studies on single crystals of peptide 1 reveal a β-hairpin conformation in both the molecules, which constitute the crystallographic asymmetric unit. Three cross-strand hydrogen bonds and a nucleating type II′ β-turn at the D-Pro-Gly segment are observed in the two independent molecules. In peptide 1, the Phe residues at positions 2 and 7 occur at the nonhydrogen-bonding position, with the benzyl side chains pointing on opposite faces of the β-sheet. The observed aromatic centroid-to-centroid distances are 8.92 Å (molecule A) and 8.94 Å (molecule B). In peptide 2, the aromatic rings must occupy facing positions in antiparallel strands, in the NMR-derived structure. Peptide 1 yields a normal hairpin-like CD spectrum in methanol with a minimum at 224 nm. The CD spectrum of peptide 2 reveals a negative band at 234 nm and a positive band at 221 nm, suggestive of an exciton split doublet. Modeling of the facing Phe side chains at the hydrogen-bonding position of a canonical β-hairpin suggests that interring separation is 4.78 Å for the gauche+gauche- (g+g-) rotamer. A previously reported peptide β-hairpin composed of only α-amino acids, Boc-Leu-Phe-Val-D-Pro-Gly-Leu-Phe-Val-OMe also exhibited an anomalous far-UV (ultraviolet) CD (circular dichroism) spectrum, which was interpreted in terms of interactions between facing aromatic chromophores, Phe 2 and Phe 7

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons, Inc.
Keywords:Peptide Hairpins; Hybrid Peptides; β-peptides; Anomalous Circular Dichroism; Cross-strand Aromatic Interactions; Exciton Split Doublet; Peptide Crystal Structure
ID Code:4696
Deposited On:18 Oct 2010 07:03
Last Modified:16 May 2016 15:18

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