抗P-糖蛋白多肽模拟物的设计、合成与活性评价

Structure-based design, synthesis and evaluation of bioactivity of anti-P-gp peptide mimetic

目的 设计、合成抗P 糖蛋白抗体 (PHMA0 2 )的多肽模拟物 ,测定其与P gp结合活性。方法 模建出PHMA0 2的互补决定簇 (complementarity determiningregion ,CDR)三维结构 ,构建出抗P gp的多肽模拟物。流式细胞仪测定其活性。结果 该模拟物竞争P gp抗体与P gp结合 ,并部分阻断P gp药物外排泵的功能。结果显示抗P gp肽模拟物对P gp具有相同结合活性。结论 根据抗体CDR区的构象特征可以构建具有生物活性的肽模拟物。

Aim To design and evaluate the small peptide mimetic of anti-P-glycoprotein ( P-gp ) antibody (PHMA02 ). Methods From the three dementional structure analysis of computer modeling of PHMA02 CDR loops, a small peptide mimetic was designed and determined by flow cytometry. Results Anti-P-gp peptide mimetic functionally similar to PHMA02 was developed. The peptide mimetic competitively inhibits PHMA02 binding to P-gp and partially block the P-gp function as a drug efflux pump in K562/A02 cells. Conclusion ...