使用磷酸酪氨酸模拟物氟代O-丙二酰酪氨酸（FOMT）对蛋白酪氨酸磷酸酶-1B进行强效抑制。

Potent inhibition of protein-tyrosine phosphatase-1B using the phosphotyrosyl mimetic fluoro-O-malonyl tyrosine (FOMT).

作者信息

Roller P P, Wu L, Zhang Z Y, Burke T R

机构信息

Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Bioorg Med Chem Lett. 1998 Aug 18;8(16):2149-50. doi: 10.1016/s0960-894x(98)00376-x.

DOI:10.1016/s0960-894x(98)00376-x

PMID:9873503

Abstract

To enhance PTP binding interactions, both inside and outside the pTyr binding pocket, a thioether-cyclized peptide has been designed based on the EGF receptor autophosphorylation sequence (EGFR988-993) "Asp-Ala-Asp-Glu-pTyr-Leu", in which the pTyr resiude has been replaced by the nonphosphorus-containing pTyr mimetic fluoro-O-malonyltyrosine (FOMT, 2). The resulting peptide 4 exhibits a Ki value of 170 nM, making it one of the most potent inhibitors of PTP1B yet reported.

摘要

为增强PTP结合相互作用，在磷酸化酪氨酸（pTyr）结合口袋内外，基于表皮生长因子受体（EGF受体）自身磷酸化序列（EGFR988 - 993）“Asp - Ala - Asp - Glu - pTyr - Leu”设计了一种硫醚环化肽，其中pTyr残基已被不含磷的pTyr模拟物氟代O - 丙二酰酪氨酸（FOMT，2）取代。所得肽4的抑制常数（Ki）值为170 nM，使其成为迄今报道的最有效的蛋白酪氨酸磷酸酶1B（PTP1B）抑制剂之一。