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

Department of Pharmacy

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
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 - 8 Apr 2004

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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.\}",

year = "2004",

month = apr,

day = "8",

doi = "10.1021/jm030510e",

language = "English",

volume = "47",

pages = "2166--2169",

journal = "Journal of Medicinal Chemistry",

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TY - JOUR

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.

UR - https://www.scopus.com/pages/publications/11144358219

U2 - 10.1021/jm030510e

DO - 10.1021/jm030510e

M3 - Article

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AN - SCOPUS:11144358219

SN - 0022-2623

VL - 47

SP - 2166

EP - 2169

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 8

ER -

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

Abstract

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