Tuning the β-turn segment in designed peptide β-hairpins: Construction of a stable type I′ β-turn nucleus and hairpin–helix transition promoting segments
✍ Scribed by Rajkishor Rai; Srinivasarao Raghothama; Rajagopalan Sridharan; Padmanabhan Balaram
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 2007
- Tongue
- English
- Weight
- 553 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0006-3525
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✦ Synopsis
Abstract
Designed octapeptides Boc‐Leu‐Val‐Val‐Aib‐^D^Xxx‐Leu‐Val‐Val‐OMe (^D^Xxx = ^D^Ala, 3a;^D^Val, 3c and ^D^Pro, 5a) and Boc‐Leu‐Phe‐Val‐Aib‐^D^Ala‐Leu‐Phe‐Val‐OMe (3b) have been investigated to construct models of a stable type I′ β‐turn nucleated hairpin and to generate systems for investigating helix–hairpin conformational transitions. Peptide 5a, which contains a central Aib‐^D^Pro segment, is shown to adopt a stable type I′ β‐turn nucleated hairpin structure, stabilized by four cross‐strand hydrogen bonds. The stability of the structure in diverse solvents is established by the observation of all diagnostic NOEs expected in a β‐hairpin conformation. Replacement of ^D^Pro5 by ^D^Ala/^D^Val (3a–c) results in sequences that form β‐hairpins in hydrogen bonding solvents like CD~3~OH and DMSO‐d~6~. However, in CDCl~3~ evidence for population of helical conformations is obtained. Peptide 6b (Boc‐Leu‐Phe‐Val‐Aib‐Aib‐Leu‐Phe‐Val‐OMe), which contains a centrally positioned Aib‐Aib segment, provides a clear example of a system, which exhibits a helical conformation in CDCl~3~ and a significant population of both helices and hairpins in CD~3~OH and DMSO‐d~6~. The coexistence of multiple conformations is established by the simultaneous observation of diagnostic NOEs. Control over stereochemistry of the central β‐turn permits generation of models for robust β‐hairpins and also for the construction of systems that may be used to probe helix–hairpin conformational transitions. © 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 350–361, 2007.
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