Synthesis of a 5-methylindolyl-containing macrocycle that displays ultrapotent Grb2 SH2 domain-binding affinity.
J Med Chem
; 47(4): 788-91, 2004 Feb 12.
Article
em En
| MEDLINE
| ID: mdl-14761181
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.
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Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Domínios de Homologia de src
/
Indóis
/
Antineoplásicos
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article