Synthesis of a 5-methylindolyl-containing macrocycle that displays ultrapotent Grb2 SH2 domain-binding affinity.
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Shi ZD, Lee K, Wei CQ, Roberts LR, Worthy KM, Fisher RJ, Burke TR Jr
Synthesis of a 5-methylindolyl-containing macrocycle that displays ultrapotent Grb2 SH2 domain-binding affinity.
J Med Chem. 2004 Feb 12;47(4):788-91.
- PubMed ID
- 14761181 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 4-[(10s,14s,18s)-18-(2-Amino-2-Oxoethyl)-14-(1-Naphthylmethyl)-8,17,20-Trioxo-7,16,19-Triazaspiro[5.14]Icos-11-En-10-Yl]Benzylphosphonic Acid Growth factor receptor-bound protein 2 IC 50 (nM) 20 N/A N/A Details