School of Pharmacy, and Key Laboratory for Advanced Material and Fine Chemicals, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China.
Eur J Med Chem. 2011 Sep;46(9):4212-8. doi: 10.1016/j.ejmech.2011.06.025. Epub 2011 Jun 25.
With an aim of developing novel protein tyrosine phosphatase (PTP) 1B inhibitors based on sugar scaffolds, a focused library of benzyl 6-triazolo(hydroxy)benzoic glucosides was efficiently constructed via the modular and selective Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddtion (click chemistry). These glycoconjugates bearing alkyl chain length-varied bridges between the sugar and (hydroxy)-benzoic moieties were identified as new PTP1B inhibitors with selectivity over T-Cell PTP (TCPTP), SH2-Containing PTP-1 (SHP-1), SHP-2 and Leukocyte Antigen-Related Tyrosine Phosphatase (LAR). Molecular docking study sequentially elaborated the plausible binding modes of the structurally diverse sugar-based inhibitors with PTP1B.
为了基于糖支架开发新型蛋白酪氨酸磷酸酶 1B（PTP1B）抑制剂，通过模块化和选择性铜（I）催化叠氮-炔 1,3-偶极环加成（点击化学），高效构建了苯并三唑（hydroxy）苯甲酸苄基葡萄糖苷的聚焦文库。这些糖和（hydroxy）苯甲酸部分之间带有烷基链长度变化桥的糖缀合物被鉴定为新型 PTP1B 抑制剂，对 T 细胞 PTP（TCPTP）、含 SH2 的 PTP-1（SHP-1）、SHP-2 和白细胞相关酪氨酸磷酸酶（LAR）具有选择性。分子对接研究依次阐述了结构多样的糖基抑制剂与 PTP1B 的可能结合模式。
