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Bioorg Med Chem. 1995 Sep;3(9):1263-72.

Structure-activity studies of phosphorylated peptide inhibitors of the association of phosphatidylinositol 3-kinase with PDGF-beta receptor.

Author information

1
Department of Chemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.

Abstract

Phosphorylated pentapeptides derived from Tyr751 of the PDGF-beta receptor (pTyr751-Val-Pro-Met-Leu, pTyr = phosphotyrosine) were prepared to examine their ability to inhibit the association of the C-terminal SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) with the PDGF-beta receptor. Peptidic analogs were prepared to examine the importance of the amine and carboxy terminus and specific amino acids via alanine/D-amino acid scans and site specific modifications. Several of these peptides had submicromolar activity. In particular, it was shown that neutralization of the amine and carboxy terminus led to analogs with enhanced activity. In addition, it was determined that only minimal modifications were allowed for pTyr and Met, while the other positions were quite tolerant of modification.

PMID:
8564419
[Indexed for MEDLINE]

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