1. Peptide hairpins with strand segments containing α- and β-amino acid residues: Cross-strand aromatic interactions of facing Phe residues
- Author
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Srinivasarao Raghothama, Hosahudya N. Gopi, Isabella L. Karle, Rituparna Sinha Roy, Richard Gilardi, and Padmanabhan Balaram
- Subjects
Models, Molecular ,Spectrometry, Mass, Electrospray Ionization ,Circular dichroism ,Protein Conformation ,Stereochemistry ,Phenylalanine ,Population ,Molecular Conformation ,Biophysics ,Peptide ,Crystallography, X-Ray ,Antiparallel (biochemistry) ,Biochemistry ,Article ,Protein Structure, Secondary ,Biomaterials ,Protein structure ,X-Ray Diffraction ,Amino Acid Sequence ,Amino Acids ,education ,Nuclear Magnetic Resonance, Biomolecular ,Peptide sequence ,Chromatography, High Pressure Liquid ,chemistry.chemical_classification ,education.field_of_study ,Hydrogen bond ,Chemistry ,Circular Dichroism ,Organic Chemistry ,Hydrogen Bonding ,Stereoisomerism ,General Medicine ,Amino acid ,Molecular Weight ,Models, Chemical ,Oligopeptides ,Protein Binding - Abstract
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-Leu-betaPhe-Val-(D)-Pro-Gly-Leu-betaPhe-Val-OMe (1) and Boc-betaLeu-Phe-betaVal-D-Pro-Gly-betaLeu-Phe-betaVal-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 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 betaPhe 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 A (molecule A) and 8.94 A (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 beta-hairpin suggests that interring separation is approximately 4.78 A for the gauche+ gauche- (g+ g-) rotamer. A previously reported peptide beta-hairpin composed of only alpha-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 (C. Zhao, P. L. Polavarapu, C. Das, and P. Balaram, Journal of the American Chemical Society, 2000, Vol 122, pp. 8228-8231).
- Published
- 2005
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