Solid-phase synthesis of short Î ±-helices stabilized by the hydrogen bond surrogate approach

Anupam Patgiri, Monica Z. Menzenski, Andrew B. Mahon, Paramjit Arora

Research output: Contribution to journalArticle

Abstract

Stabilized Î ±-helices and nonpeptidic helix mimetics have emerged as powerful molecular scaffolds for the discovery of proteing-protein interaction inhibitors. Protein-protein interactions often involve large contact areas, which are often difficult for small molecules to target with high specificity. The hypothesis behind the design of stabilized helices and helix mimetics is that these medium-sized molecules may pursue their targets with higher specificity because of a larger number of contacts. This protocol describes an optimized synthetic strategy for the preparation of stabilized Î ±-helices that feature a carbon-carbon linkage in place of the characteristic N-terminal main-chain hydrogen bond of canonical helices. Formation of the carbon-carbon bond is enabled by a microwave-assisted ring-closing metathesis reaction between two terminal olefins on the peptide chain. The outlined strategy allows the synthesis and purification of a hydrogen bond surrogate (HBS) Î ±-helix in ĝ̂1/41 week.

Original languageEnglish (US)
Pages (from-to)1857-1865
Number of pages9
JournalNature Protocols
Volume5
Issue number11
DOIs
StatePublished - Oct 2010

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Solid-Phase Synthesis Techniques
Hydrogen
Hydrogen bonds
Carbon
Proteins
Molecules
Alkenes
Microwaves
Scaffolds
Purification
Peptides

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Solid-phase synthesis of short Î ±-helices stabilized by the hydrogen bond surrogate approach. / Patgiri, Anupam; Menzenski, Monica Z.; Mahon, Andrew B.; Arora, Paramjit.

In: Nature Protocols, Vol. 5, No. 11, 10.2010, p. 1857-1865.

Research output: Contribution to journalArticle

Patgiri, Anupam ; Menzenski, Monica Z. ; Mahon, Andrew B. ; Arora, Paramjit. / Solid-phase synthesis of short Î ±-helices stabilized by the hydrogen bond surrogate approach. In: Nature Protocols. 2010 ; Vol. 5, No. 11. pp. 1857-1865.
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