Left- and right-handed alpha-helical turns in homo- and hetero-chiral helical scaffolds

Shepherd, N. E., Hoang, H. N., Abbenante, G and Fairlie, D. P. (2009) Left- and right-handed alpha-helical turns in homo- and hetero-chiral helical scaffolds. Journal of the American Chemical Society, 131 43: 15877-15886. doi:10.1021/ja9065283

Author Shepherd, N. E.
Hoang, H. N.
Abbenante, G
Fairlie, D. P.
Title Left- and right-handed alpha-helical turns in homo- and hetero-chiral helical scaffolds
Journal name Journal of the American Chemical Society   Check publisher's open access policy
ISSN 0002-7863
Publication date 2009-11-01
Year available 2009
Sub-type Article (original research)
DOI 10.1021/ja9065283
Open Access Status Not Open Access
Volume 131
Issue 43
Start page 15877
End page 15886
Total pages 10
Editor Peter J Stang
Place of publication Washington , D.C., U.S.A.
Publisher American Chemical Society
Language eng
Subject C1
8608 Human Pharmaceutical Products
860899 Human Pharmaceutical Products not elsewhere classified
039999 Chemical Sciences not elsewhere classified
Abstract Proteins typically consist of right-handed alpha helices, whereas left-handed alpha helices are rare in nature. Peptides of 20 amino acids or less corresponding to protein helices do not form thermodynamically stable alpha helices in water away from protein environments. The smallest known water-stable right- (αR) and left- (αL) handed alpha helices are reported, each stabilized in cyclic pentapeptide units containing all L- or all D-amino acids. Homochiral decapeptides comprising two identical cyclic pentapeptides (αRαR or αLαL) are continuous alpha-helical structures that are extremely stable to denaturants, degradative proteases, serum, and additives like TFE, acid, and base. Heterochiral decapeptides comprising two different cyclic pentapeptides (αLαR or αRαL) maintain the respective helical handedness of each monocyclic helical turn component but adopt extended or bent helical structures depending on the solvent environment. Adding TFE to their aqueous solutions caused a change to bent helical structures with slightly distorted N-terminal αR or αL-helical turns terminated by a Schellman-like motif adjacent to the C-terminal αL or αR-turn. This hinge-like switching between structures in response to an external cue suggests possible uses in larger structures to generate smart materials. The library of left- and right-handed 1−3 turn alpha-helical compounds reported herein project their amino acid side chains into very different regions of 3D space, constituting a unique and potentially valuable class of novel scaffolds.
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 15 times in Scopus Article | Citations
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Created: Sun, 22 Nov 2009, 10:02:34 EST