[EN] METHODS AND SYSTEMS FOR PREPARING IRREVERSIBLE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASES<br/>[FR] PROCÉDÉS ET SYSTÈMES POUR PRÉPARER DES INHIBITEURS IRRÉVERSIBLES DE PROTÉINES TYROSINES PHOSPHATASES
申请人:UNIV ALBERTA
公开号:WO2011106898A1
公开(公告)日:2011-09-09
Described herein are the preparation and use of novel bromo- phosphonomethylphenylalanine amino acid derivatives (BrPmp) and BrPmp-containing peptides as specific, irreversible protein tyrosine phosphatase inhibitors, which are suitable for application in peptide synthesis. These derivatives are particularly advantageous since their synthesis is both easy and scalable, and they are suitable for peptide synthesis. The BrPmp derivatives described herein can be appropriately protected to allow for solid phase peptide synthesis (SPPS) and incorporation into peptides for preparation of protein tyrosine phosphatase inhibitors and inhibitor libraries. The peptides and peptide libraries can be used to identify new protein tyrosine phosphatase specific sequences and profile protein tyrosine phosphatase activity in cell lysates, diagnostic samples and biopsy samples.
在本发明中,描述了新颖的溴代磷酰甲基苯丙氨酸氨基酸衍生物(BrPmp)及其含BrPmp肽段的制备和应用,这些衍生物是特异性的、不可逆的蛋白酪氨酸磷酸酶抑制剂,适用于肽合成中的应用。这些衍生物的合成既简单又可放大,适合于肽合成。所述的BrPmp衍生物可以适当地进行保护,以便进行固相肽合成(SPPS)并并入肽中,用于制备蛋白酪氨酸磷酸酶抑制剂和抑制剂库。所得到的肽和肽库可用于识别新的蛋白酪氨酸磷酸酶特异序列,并在细胞裂解液、诊断样本和活检样本中分析蛋白酪氨酸磷酸酶的活性。