Abstract
The growth factor receptor-bound protein 2 (Grb2) is an SH2 domain-containing docking module that represents an attractive target for anticancer therapeutic intervention. Here, a ring-closing metathesis approach is utilized to synthesize a 5-methylindolyl-containing tetrapeptide mimetic (6) that exhibits unprecedented in vitro Grb2 SH2 domain-binding affinity (K d = 93 pM). Key to the preparation of 6 is the enantioselective synthesis of (2S)-2-(3-(5-methylindolyl)methyl)pent-4-enylamine (12) as one of two ring-closing segments.
Original language | English |
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Pages (from-to) | 788-791 |
Number of pages | 4 |
Journal | Journal of Medicinal Chemistry |
Volume | 47 |
Issue number | 4 |
DOIs | |
State | Published - 12 Feb 2004 |