Synthesis of a 5-Methylindolyl-Containing Macrocycle That Displays Ultrapotent Grb2 SH2 Domain-Binding Affinity
2004
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.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
5
References
26
Citations
NaN
KQI