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 |
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Pages (from-to) | 2166-2169 |
Number of pages | 4 |
Journal | Journal of Medicinal Chemistry |
Volume | 47 |
Issue number | 8 |
DOIs | |
State | Published - 8 Apr 2004 |