In the established nomenclature for stapled peptides2Si,i+4S(8) refers to an eight carbon crosslink between S configurated α-substituted amino acids at positions “i” and “i+4”, respectively. Similarly, Ri,i+7S(11) peptide refers to 11 carbon crosslink between α-substituted amino acids with R configuration at “i” and S configuration at “i+7” positions, respectively.
Version of Record online: 14 DEC 2011
Copyright © 2011 Wiley Periodicals, Inc.
Volume 97, Issue 5, pages 253–264, May 2012
How to Cite
Bhattacharya, S., Zhang, H., Cowburn, D., Debnath, A. K. (2012), Novel structures of self-associating stapled peptides. Biopolymers, 97: 253–264. doi: 10.1002/bip.22015
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley. com
- Issue online: 21 FEB 2012
- Version of Record online: 14 DEC 2011
- Manuscript Accepted: 1 DEC 2011
- Manuscript Revised: 30 NOV 2011
- Manuscript Received: 6 SEP 2011
- NIH. Grant Number: RO1 AI081604
- NIH. Grant Number: GM-47021, GM-66356
- the intramural fund from the New York Blood Center, Keck Foundation, NYSBC
- stapled peptides;
Hydrocarbon stapling of peptides is a powerful technique to transform linear peptides into cell-permeable helical structures that can bind to specific biological targets. In this study, we have used high resolution solution NMR techniques complemented by dynamic light scattering to characterize extensively a family of hydrocarbon stapled peptides with known inhibitory activity against HIV-1 capsid assembly to evaluate the various factors that modulate activity. The helical peptides share a common binding motif but differ in charge, the length, and position of the staple. An important outcome of the study was to show the peptides, share a propensity to self-associate into organized polymeric structures mediated predominantly by hydrophobic interactions between the olefinic chain and the aromatic side-chains from the peptide. We have also investigated in detail the structural significance of the length and position of the staple, and of olefinic bond isomerization in stabilizing the helical conformation of the peptides as potential factors driving polymerization. This study presents the numerous challenges of designing biologically active stapled peptides and the conclusions have broad implications for optimizing a promising new class of compounds in drug discovery. © 2011 Wiley Periodicals, Inc. Biopolymers 97: 253–264, 2012.