Bioorganic & Medicinal Chemistry Letters 2000-10-16

Structure-based design and synthesis of phosphinate isosteres of phosphotyrosine for incorporation in Grb2-SH2 domain inhibitors. Part 1.

P Furet, G Caravatti, A A Denholm, A Faessler, H Fretz, C García-Echeverría, B Gay, E Irving, N J Press, J Rahuel, J Schoepfer, C V Walker

Index: Bioorg. Med. Chem. Lett. 10 , 2337, (2000)

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Abstract

Based on X-ray crystal structure information, mono charged phosphinate isosteres of phosphotyrosine have been designed and incorporated in a short inhibitory peptide sequence of the Grb2-SH2 domain. The resulting compounds, by exploiting additional interactions, inhibit binding to the Grb2-SH2 domain as potently as the corresponding doubly charged (phosphonomethyl)phenylalanine analogue.