Computational design of a β-peptide that targets transmembrane helices

Scott J. Shandler; Ivan V. Korendovych; David T. Moore; Kathryn B. Smith-Dupont; Craig N. Streu; Rustem I. Litvinov; Paul C. Billings; Feng Gai; Joel S. Bennett; William F. Degrado

doi:10.1021/ja204215f

Computational design of a β-peptide that targets transmembrane helices

Scott J. Shandler, Ivan V. Korendovych, David T. Moore, Kathryn B. Smith-Dupont, Craig N. Streu, Rustem I. Litvinov, Paul C. Billings, Feng Gai, Joel S. Bennett, William F. Degrado

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

The design of β-peptide foldamers targeting the transmembrane (TM) domains of complex natural membrane proteins has been a formidable challenge. A series of β-peptides was designed to stably insert in TM orientations in phospholipid bilayers. Their secondary structures and orientation in the phospholipid bilayer was characterized using biophysical methods. Computational methods were then devised to design a β-peptide that targeted a TM helix of the integrin α _IIbβ ₃. The designed peptide (β-CHAMP) interacts with the isolated target TM domain of the protein and activates the intact integrin in vitro.

Original language	English (US)
Pages (from-to)	12378-12381
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	133
Issue number	32
DOIs	https://doi.org/10.1021/ja204215f
State	Published - Aug 17 2011
Externally published	Yes

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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10.1021/ja204215f

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title = "Computational design of a β-peptide that targets transmembrane helices",

abstract = "The design of β-peptide foldamers targeting the transmembrane (TM) domains of complex natural membrane proteins has been a formidable challenge. A series of β-peptides was designed to stably insert in TM orientations in phospholipid bilayers. Their secondary structures and orientation in the phospholipid bilayer was characterized using biophysical methods. Computational methods were then devised to design a β-peptide that targeted a TM helix of the integrin α IIbβ 3. The designed peptide (β-CHAMP) interacts with the isolated target TM domain of the protein and activates the intact integrin in vitro.",

author = "Shandler, {Scott J.} and Korendovych, {Ivan V.} and Moore, {David T.} and Smith-Dupont, {Kathryn B.} and Streu, {Craig N.} and Litvinov, {Rustem I.} and Billings, {Paul C.} and Feng Gai and Bennett, {Joel S.} and Degrado, {William F.}",

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T1 - Computational design of a β-peptide that targets transmembrane helices

AU - Shandler, Scott J.

AU - Korendovych, Ivan V.

AU - Moore, David T.

AU - Smith-Dupont, Kathryn B.

AU - Streu, Craig N.

AU - Litvinov, Rustem I.

AU - Billings, Paul C.

AU - Gai, Feng

AU - Bennett, Joel S.

AU - Degrado, William F.

PY - 2011/8/17

Y1 - 2011/8/17

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AB - The design of β-peptide foldamers targeting the transmembrane (TM) domains of complex natural membrane proteins has been a formidable challenge. A series of β-peptides was designed to stably insert in TM orientations in phospholipid bilayers. Their secondary structures and orientation in the phospholipid bilayer was characterized using biophysical methods. Computational methods were then devised to design a β-peptide that targeted a TM helix of the integrin α IIbβ 3. The designed peptide (β-CHAMP) interacts with the isolated target TM domain of the protein and activates the intact integrin in vitro.

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Computational design of a β-peptide that targets transmembrane helices

Abstract

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