Abstract：
:Stabilized α-helices and nonpeptidic helix mimetics have emerged as powerful molecular scaffolds for the discovery of protein-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 α-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) α-helix in ∼ 1 week.
journal_name
Nat Protocjournal_title
Nature protocolsauthors
Patgiri A,Menzenski MZ,Mahon AB,Arora PSdoi
10.1038/nprot.2010.146subject
Has Abstractpub_date
2010-11-01 00:00:00pages
1857-65issue
11eissn
1754-2189issn
1750-2799pii
nprot.2010.146journal_volume
5pub_type
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