Macrocyclization in the Design of Non-Phosphorus-Containing Grb2 SH2 Domain-Binding Ligands

Zhen Dan Shi; Chang Qing Wei; Kyeong Lee; Hongpeng Liu; Manchao Zhang; Toshiyuki Araki; Lindsey R. Roberts; Karen M. Worthy; Robert J. Fisher; Benjamin G. Neel; James A. Kelley; Dajun Yang; Terrence R. Burke

doi:10.1021/jm030510e

Macrocyclization in the Design of Non-Phosphorus-Containing Grb2 SH2 Domain-Binding Ligands

Zhen Dan Shi, Chang Qing Wei, Kyeong Lee, Hongpeng Liu, Manchao Zhang, Toshiyuki Araki, Lindsey R. Roberts, Karen M. Worthy, Robert J. Fisher, Benjamin G. Neel, James A. Kelley, Dajun Yang, Terrence R. Burke

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

34 Scopus citations

Abstract

Macrocyclization from the phosphotyrosyl (pTyr) mimetic's β-position has previously been shown to enhance Grb2 SH2 domain-binding affinity of phosphonate-based analogues. The current study examined the effects of such macrocyclization using a dicarboxymethyl-based pTyr mimetic. In extracellular assays affinity was enhanced approximately 5-fold relative to an open-chain congener. Enhancement was also observed in whole-cell assays examining blockade of Grb2 binding to the erbB-2 protein-tyrosine kinase.

Original language	English (US)
Pages (from-to)	2166-2169
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	47
Issue number	8
DOIs	https://doi.org/10.1021/jm030510e
State	Published - Apr 8 2004

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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title = "Macrocyclization in the Design of Non-Phosphorus-Containing Grb2 SH2 Domain-Binding Ligands",

abstract = "Macrocyclization from the phosphotyrosyl (pTyr) mimetic's β-position has previously been shown to enhance Grb2 SH2 domain-binding affinity of phosphonate-based analogues. The current study examined the effects of such macrocyclization using a dicarboxymethyl-based pTyr mimetic. In extracellular assays affinity was enhanced approximately 5-fold relative to an open-chain congener. Enhancement was also observed in whole-cell assays examining blockade of Grb2 binding to the erbB-2 protein-tyrosine kinase.",

author = "Shi, {Zhen Dan} and Wei, {Chang Qing} and Kyeong Lee and Hongpeng Liu and Manchao Zhang and Toshiyuki Araki and Roberts, {Lindsey R.} and Worthy, {Karen M.} and Fisher, {Robert J.} and Neel, {Benjamin G.} and Kelley, {James A.} and Dajun Yang and Burke, {Terrence R.}",

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language = "English (US)",

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T1 - Macrocyclization in the Design of Non-Phosphorus-Containing Grb2 SH2 Domain-Binding Ligands

AU - Shi, Zhen Dan

AU - Wei, Chang Qing

AU - Lee, Kyeong

AU - Liu, Hongpeng

AU - Zhang, Manchao

AU - Araki, Toshiyuki

AU - Roberts, Lindsey R.

AU - Worthy, Karen M.

AU - Fisher, Robert J.

AU - Neel, Benjamin G.

AU - Kelley, James A.

AU - Yang, Dajun

AU - Burke, Terrence R.

PY - 2004/4/8

Y1 - 2004/4/8

N2 - Macrocyclization from the phosphotyrosyl (pTyr) mimetic's β-position has previously been shown to enhance Grb2 SH2 domain-binding affinity of phosphonate-based analogues. The current study examined the effects of such macrocyclization using a dicarboxymethyl-based pTyr mimetic. In extracellular assays affinity was enhanced approximately 5-fold relative to an open-chain congener. Enhancement was also observed in whole-cell assays examining blockade of Grb2 binding to the erbB-2 protein-tyrosine kinase.

AB - Macrocyclization from the phosphotyrosyl (pTyr) mimetic's β-position has previously been shown to enhance Grb2 SH2 domain-binding affinity of phosphonate-based analogues. The current study examined the effects of such macrocyclization using a dicarboxymethyl-based pTyr mimetic. In extracellular assays affinity was enhanced approximately 5-fold relative to an open-chain congener. Enhancement was also observed in whole-cell assays examining blockade of Grb2 binding to the erbB-2 protein-tyrosine kinase.

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Macrocyclization in the Design of Non-Phosphorus-Containing Grb2 SH2 Domain-Binding Ligands

Abstract

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