Structure-Activity Studies of Phosphorylated Peptide Inhibitors of the Association of Phosphatidylinositol 3-Kinase with PDGF-β Receptor

详细信息    查看全文

• 作者：Ramalingam ; Kalaiyarasi ; Eaton ; Scott R. ; Cody ; Wayne L. ; Lu ; Gina H. ; Panek ; Robert L. ; Waite ; Lisa A. ; et. al.
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：1995
• 出版时间：September, 1995
• 年：1995
• 卷：3
• 期：9
• 页码：1263-1272
• 全文大小：869 K

文摘

Phosphorylated pentapeptides derived from Tyr⁷⁵¹ of the PDGF-β 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-β 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.