Novel structures of self-associating stapled peptides

Shibani Bhattacharya, Hongtao Zhang, David Cowburn, Asim K. Debnath

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)253-264
Number of pages12
JournalBiopolymers
Volume97
Issue number5
DOIs
StatePublished - May 2012

Fingerprint

Peptides
Hydrocarbons
Capsid
Dynamic light scattering
Drug Discovery
Isomerization
Hydrophobic and Hydrophilic Interactions
Polymerization
Conformations
HIV-1
Nuclear magnetic resonance
Outcome Assessment (Health Care)

Keywords

  • HIV-capsid
  • NMR
  • stapled peptides

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Biomaterials
  • Organic Chemistry

Cite this

Bhattacharya, S., Zhang, H., Cowburn, D., & Debnath, A. K. (2012). Novel structures of self-associating stapled peptides. Biopolymers, 97(5), 253-264. https://doi.org/10.1002/bip.22015

Novel structures of self-associating stapled peptides. / Bhattacharya, Shibani; Zhang, Hongtao; Cowburn, David; Debnath, Asim K.

In: Biopolymers, Vol. 97, No. 5, 05.2012, p. 253-264.

Research output: Contribution to journalArticle

Bhattacharya, S, Zhang, H, Cowburn, D & Debnath, AK 2012, 'Novel structures of self-associating stapled peptides', Biopolymers, vol. 97, no. 5, pp. 253-264. https://doi.org/10.1002/bip.22015
Bhattacharya, Shibani ; Zhang, Hongtao ; Cowburn, David ; Debnath, Asim K. / Novel structures of self-associating stapled peptides. In: Biopolymers. 2012 ; Vol. 97, No. 5. pp. 253-264.
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