Hybrid Peptides: Expanding the \beta Turn in Peptide Hairpins by the Insertion of \beta-, \gamma-, and \delta-Residues

Rai, Rajkishor and Vasudev, Prema G and Ananda, Kuppanna and Raghothama, Srinivasarao and Shamala, Narayanaswamy and Karle, Isabella L and Balaram, Padmanabhan (2007) Hybrid Peptides: Expanding the \beta Turn in Peptide Hairpins by the Insertion of \beta-, \gamma-, and \delta-Residues. In: Chemistry - A European Journal, 13 (20). pp. 5917-5926.

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Abstract

The \beta turn segment in designed peptide hairpins has been expanded by the insertion of \beta-, \gamma- and \delta amino acids at the i+2 position. The model octapeptides Boc-Leu-Phe-Val-$^D$Pro-$Ac_6c$-Leu-Phe-Val-OMe (1), Boc-Leu-Phe-Val-$^D$Pro-$\beta^3$-$Ac_6c$-Leu-Phe-Val-OMe (2),and Boc-Leu-Phe-Val-$^D$Pro-Gpn-Leu-Phe-Val-OMe (3) have been shown to adopt \beta hairpin conformations in methanol by the observation of key diagnostic nuclear Overhauser effects. Boc-Leu-Val-Val-$^D$dPro-\delta-Ava-Leu-Val-Val-OMe (4) adopts a \beta hairpin conformation in crystals; this is stabilized by three cross-strand hydrogen bonds as demonstrated by X-ray diffraction. The canonical $C_{10}$ turn in an \alpha–\alpha segment is expanded to $C_{11}$, $C_{12}$,and $C_{13}$ turns in \alpha–\beta, \alpha–\gamma, and \alpha–\delta segments,respectively. The crystal structures of Piv-$^L$Pro-$\beta^3$-$Ac_6c$-NHMe (5) and Boc-$Ac_6c$-Gpn-$Ac_6c$-OMe (6) reveal intramolecularly hydrogen-bonded $C_{11}$ and $C_{12}$ conformations, respectively. Computer modeling of octapeptide sequences that contain centrally positioned hybrid-turn segments, by using turn parameters derived from the structures of peptides 5 and 6,establishes the stereochemical acceptability of the \beta hairpins in the cases of peptides 2 and 3. Accommodation of $\omega$-amino acids into the turn segments is achieved by the adoption of gauche conformations around the backbone $C - C$ bonds.

Item Type:	Journal Article
Publication:	Chemistry - A European Journal
Publisher:	John Wiley & Sons, Inc.
Additional Information:	Copyright of this article belongs to John Wiley & Sons, Inc.
Keywords:	amino acids;beta hairpins;peptides;structure elucidation
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Physical & Mathematical Sciences > Physics
Date Deposited:	06 Jun 2008
Last Modified:	19 Sep 2010 04:45
URI:	http://eprints.iisc.ac.in/id/eprint/14219

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