Design and structure of stapled peptides binding to estrogen receptors

Chris Phillips; Lee R. Roberts; Markus Schade; Richard Bazin; Andrew Bent; Nichola L. Davies; Rob Moore; Andrew D. Pannifer; Andrew R. Pickford; Stephen H. Prior; Christopher M. Read; Andrew Scott; David G. Brown; Bin Xu; Stephen L. Irving

doi:10.1021/ja202946k

Design and structure of stapled peptides binding to estrogen receptors

Chris Phillips, Lee R. Roberts, Markus Schade, Richard Bazin, Andrew Bent, Nichola L. Davies, Rob Moore, Andrew D. Pannifer, Andrew R. Pickford, Stephen H. Prior, Christopher M. Read, Andrew Scott, David G. Brown, Bin Xu, Stephen L. Irving

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

Abstract

Synthetic peptides that specifically bind nuclear hormone receptors offer an alternative approach to small molecules for the modulation of receptor signaling and subsequent gene expression. Here we describe the design of a series of novel stapled peptides that bind the coactivator peptide site of estrogen receptors. Using a number of biophysical techniques, including crystal structure analysis of receptor–stapled peptide complexes, we describe in detail the molecular interactions and demonstrate that all-hydrocarbon staples modulate molecular recognition events. The findings have implications for the design of stapled peptides in general.

Original language	English
Pages (from-to)	9696-9699
Journal	Journal of the American Chemical Society
Volume	133
Issue number	25
DOIs	https://doi.org/10.1021/ja202946k
Publication status	Published - 29 Jun 2011

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Phillips, C., Roberts, L. R., Schade, M., Bazin, R., Bent, A., Davies, N. L., Moore, R., Pannifer, A. D., Pickford, A. R., Prior, S. H., Read, C. M., Scott, A., Brown, D. G., Xu, B., & Irving, S. L. (2011). Design and structure of stapled peptides binding to estrogen receptors. Journal of the American Chemical Society, 133(25), 9696-9699. https://doi.org/10.1021/ja202946k

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abstract = "Synthetic peptides that specifically bind nuclear hormone receptors offer an alternative approach to small molecules for the modulation of receptor signaling and subsequent gene expression. Here we describe the design of a series of novel stapled peptides that bind the coactivator peptide site of estrogen receptors. Using a number of biophysical techniques, including crystal structure analysis of receptor–stapled peptide complexes, we describe in detail the molecular interactions and demonstrate that all-hydrocarbon staples modulate molecular recognition events. The findings have implications for the design of stapled peptides in general.",

author = "Chris Phillips and Roberts, {Lee R.} and Markus Schade and Richard Bazin and Andrew Bent and Davies, {Nichola L.} and Rob Moore and Pannifer, {Andrew D.} and Pickford, {Andrew R.} and Prior, {Stephen H.} and Read, {Christopher M.} and Andrew Scott and Brown, {David G.} and Bin Xu and Irving, {Stephen L.}",

year = "2011",

month = jun,

day = "29",

doi = "10.1021/ja202946k",

language = "English",

volume = "133",

pages = "9696--9699",

journal = "Journal of the American Chemical Society",

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T1 - Design and structure of stapled peptides binding to estrogen receptors

AU - Phillips, Chris

AU - Roberts, Lee R.

AU - Schade, Markus

AU - Bazin, Richard

AU - Bent, Andrew

AU - Davies, Nichola L.

AU - Moore, Rob

AU - Pannifer, Andrew D.

AU - Pickford, Andrew R.

AU - Prior, Stephen H.

AU - Read, Christopher M.

AU - Scott, Andrew

AU - Brown, David G.

AU - Xu, Bin

AU - Irving, Stephen L.

PY - 2011/6/29

Y1 - 2011/6/29

N2 - Synthetic peptides that specifically bind nuclear hormone receptors offer an alternative approach to small molecules for the modulation of receptor signaling and subsequent gene expression. Here we describe the design of a series of novel stapled peptides that bind the coactivator peptide site of estrogen receptors. Using a number of biophysical techniques, including crystal structure analysis of receptor–stapled peptide complexes, we describe in detail the molecular interactions and demonstrate that all-hydrocarbon staples modulate molecular recognition events. The findings have implications for the design of stapled peptides in general.

AB - Synthetic peptides that specifically bind nuclear hormone receptors offer an alternative approach to small molecules for the modulation of receptor signaling and subsequent gene expression. Here we describe the design of a series of novel stapled peptides that bind the coactivator peptide site of estrogen receptors. Using a number of biophysical techniques, including crystal structure analysis of receptor–stapled peptide complexes, we describe in detail the molecular interactions and demonstrate that all-hydrocarbon staples modulate molecular recognition events. The findings have implications for the design of stapled peptides in general.

U2 - 10.1021/ja202946k

DO - 10.1021/ja202946k

M3 - Article

SN - 0002-7863

VL - 133

SP - 9696

EP - 9699

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 25

ER -

Design and structure of stapled peptides binding to estrogen receptors

Abstract

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