4.2 Article

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

Journal

BIOPOLYMERS
Volume 80, Issue 6, Pages 787-799

Publisher

WILEY
DOI: 10.1002/bip.20294

Keywords

peptide hairpins; hybrid peptides; beta-peptides; anomalous circular dichroism; cross-strand aromatic interactions; exciton split doublet; peptide crystal structure

Funding

  1. NIGMS NIH HHS [R01 GM030902-22, GM30902, R01 GM030902, R37 GM030902] Funding Source: Medline
  2. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM030902, R37GM030902] Funding Source: NIH RePORTER

Ask authors/readers for more resources

The incporation of beta-amino acid residues into the strand segments of designed beta-hairpin leads to the formation of polar sheets, since in the case of beta-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 alpha/beta-hybrid segments are described: Boc-Leti-beta Phe-Val-D-Pro-Gly-Leu-beta Phe-Val-OMe (1) and Boc-beta Leu-Phe-beta Val-D-Pro-Gly-beta Leu-Phe-beta Val-OMe (2). A 500-MHz H-1-NMR (nuclear magnetic resonance) analysis in methanol supports a significant population of hair-pin conformations in both peptides. Diagnostic nuclear Overhauser effects (NOEs) are observed in both cases. X-ray diffraction studies oil single crystals of peptide I reveal a beta-hairpin conformation in both the molecules, which constitute the crystallographic asymmetric unit. Three cross-strand hydrogen bonds and a nucleating type II' beta-turn at the D-Pro-Gly segment are observed in the two independent molecules. In peptide 1, the beta Phe residues at positions 2 and 7 occur at the nonhydrogen-bonding position. with the benzyl side chains pointing on opposite faces of the beta-sheet. The observed aromatic centroid-to-centroid distances are 8.92 angstrom (molecule angstrom) and 8.94 angstrom (molecule B). In peptide 2, the aromatic rings must occupy facing positions in antiparallel strands, hi 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 (it the hydrogen-bonding position of a canonical beta-hairpin suggests that interring separation is similar to 4.78 angstrom for the gauche(+)gauche(-) (g(+)g(-)) rotamer. A previously reported peptide beta-hairpin composed of only amino acids, Boe-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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.2
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available