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–Leu–βPhe–Val–^D^‐Pro–Gly–Leu–βPhe–Val–OMe (1) and Boc–βLeu–Phe–βVal–D‐Pro–Gly–βLeu–Phe–βVal–OMe (2). A 500‐MHz ^1^H‐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 βPhe 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 (C. Zhao, P. L. Polavarapu, C. Das, and P. Balaram, Journal of the American Chemical Society, 2000, Vol 122, pp. 8228–8231). © 2005 Wiley Periodicals, Inc. Biopoly 80: 787–799, 2005
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