Work

Synthesis of a 5-Methylindolyl-Containing Macrocycle That Displays Ultrapotent Grb2 SH2 Domain-Binding Affinity

Year: 2004

Type: article

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.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/jm030440b

Authors: Zhen-Dan Shi, Kyeong Lee, Chang-Qing Wei, Lindsey R. Roberts, Karen M. Worthy, Robert J. Fisher, Terrence R. Burke

Institutions: National Institutes of Health, National Cancer Institute, Center for Cancer Research

Language: English

Topic: Chemical Synthesis and Analysis

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

OpenAlex ID: W1980352020

FWCI: 1.98

Cites: 6

Cited by: 32

Related to: 10