Hydrophobic D-amino acids in the design of peptide ligands for the pp60src SH2 domain.
Drug Des Discov
; 13(3-4): 75-81, 1996 Apr.
Article
en En
| MEDLINE
| ID: mdl-8874045
ABSTRACT
Src homology-2 (SH2) domains, containing approximately 100 amino acid residues, are noncatalytic motifs involved with intracellular signal transduction. These domains can be found on nonreceptor kinases, phosphatases, and in regulatory adapter proteins among others. SH2 domains bind proteins containing phosphotyrosine (pTyr) residues in a sequence specific manner. Our efforts have focused on designing peptide mimetic ligands for the SH2 domain of the nonreceptor tyrosine kinase pp60src. We employed the cocrystal structure of the 11mer Glu-Pro-Gln-pTyr-Glu-Glu-Ile-Pro-IIe-Tyr-Leu IC50 = 800 nM as a starting point for our design efforts. These efforts have resulted in the discovery of tripeptide ligands containing D-amino acids that are only 2-fold less potent than the 11mer.
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Banco de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Diseño de Fármacos
/
Proteínas Proto-Oncogénicas pp60(c-src)
/
Dominios Homologos src
Idioma:
En
Revista:
Drug Des Discov
Asunto de la revista:
FARMACOLOGIA
Año:
1996
Tipo del documento:
Article
País de afiliación:
Estados Unidos