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 journalArticlepeer-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 languageEnglish
Pages (from-to)2166-2169
Number of pages4
JournalJournal of Medicinal Chemistry
Volume47
Issue number8
DOIs
StatePublished - 8 Apr 2004

Fingerprint

Dive into the research topics of 'Macrocyclization in the Design of Non-Phosphorus-Containing Grb2 SH2 Domain-Binding Ligands'. Together they form a unique fingerprint.

Cite this