Contemporary strategies for the stabilization of peptides in the alpha-helical conformation.

Abstract:

:Herein we review contemporary synthetic and protein design strategies to stabilize the alpha-helical motif in short peptides and miniature proteins. Advances in organometallic catalyst design, specifically for the olefin metathesis reaction, enable the use of hydrocarbon bridges to either crosslink side chains of specific residues or mimic intramolecular hydrogen bonds with carbon-carbon bonds. The resulting hydrocarbon-stapled and hydrogen bond surrogate alpha-helices provide unique synthetic ligands for targeting biomolecules. In the protein design realm, several classes of miniature proteins that display stable helical domains have been engineered and manipulated with powerful in vitro selection technologies to yield libraries of sequences that retain their helical folds. Rational re-design of these scaffolds provide distinctive reagents for the modulation of protein-protein interactions.

journal_name

Curr Opin Chem Biol

authors

Henchey LK,Jochim AL,Arora PS

doi

10.1016/j.cbpa.2008.08.019

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

692-7

issue

6

eissn

1367-5931

issn

1879-0402

pii

S1367-5931(08)00125-7

journal_volume

12

pub_type

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