[Difluro(phosphono)methyl]phenylalanine-containing peptide inhibitors of protein tyrosine phosphatases.
[Difluro(phosphono)methyl]phenylalanine-containing peptide inhibitors of protein tyrosine phosphatases.
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含[二氟（膦酰基）甲基]苯丙氨酸的蛋白酪氨酸磷酸酶肽抑制剂。
DOI：
10.1042/bj3370219
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
C. Ramachandran
中科院分区：
文献类型：
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作者：
S. Desmarais;R. Friesen;R. Zamboni;C. Ramachandran
合成了含有非水解磷酸酪氨酸类似物4-[二氟（膦）甲基]苯丙氨酸[Phe(CF2P)]的肽，并对其作为蛋白酪氨酸磷酸酶（PTPs） PTP1B、CD45、PTPbeta、LAR和SHP-1的抑制剂进行了测试。我们已经确定了含有两个相邻的Phe（CF2P）残基的肽作为ptp的有效抑制剂。具有Glu-Phe(CF2P)-Phe（CF2P）序列的三肽是一种有效的选择性PTP1B抑制剂。该肽抑制PTP1B的IC50为40 nM，比其他PTPs低至少100倍。第二种三肽，Pro-Phe(CF2P)-Phe(CF2P)，对PTPbeta最有效，IC50为200 nM，抑制PTP1B的IC50为300 nM。这些数据表明，有可能开发出选择性的、活性位点定向的、可逆的、有效的ptp抑制剂。
Peptides containing the non-hydrolysable phosphotyrosine analogue 4-[difluro(phosphono)methyl]phenylalanine [Phe(CF2P)] were synthesized and tested as inhibitors of the protein tyrosine phosphatases (PTPs) PTP1B, CD45, PTPbeta, LAR and SHP-1. We have identified peptides containing two adjacent Phe(CF2P) residues as potent inhibitors of PTPs. The tripeptide having the sequence Glu-Phe(CF2P)-Phe(CF2P) is a potent and selective inhibitor of PTP1B. This peptide inhibits PTP1B with an IC50 of 40 nM, which is at least 100-fold lower than with other PTPs. A second tripeptide, Pro-Phe(CF2P)-Phe(CF2P), is most potent against PTPbeta, with an IC50 of 200 nM, and inhibits PTP1B with an IC50 of 300 nM. These data suggest that it is possible to develop selective, active-site-directed, reversible, potent inhibitors of PTPs.