目的综述微管蛋白秋水仙碱结合位点抑制剂Combretastatin A-4(CA-4)类似物的研究进展。方法依据近期国内外公开发表的49篇文献,将CA-4类似物的研究进展分类、归纳并总结。结果微管蛋白秋水仙碱结合位点抑制剂(colchicine binding site i...目的综述微管蛋白秋水仙碱结合位点抑制剂Combretastatin A-4(CA-4)类似物的研究进展。方法依据近期国内外公开发表的49篇文献,将CA-4类似物的研究进展分类、归纳并总结。结果微管蛋白秋水仙碱结合位点抑制剂(colchicine binding site inhibitors,CBSI)具有增殖抑制和血管破坏双重活性,近年来备受抗肿瘤药物研究人员的关注。CA-4类似物的抗肿瘤活性突出且结构简单,是CBSI中的重要组成部分。本文对CA-4类似物的结构特点及其构效关系进行了归纳总结。结论利用CA-4类似物的构效关系归纳总结进行开发新药已成为研究热点。展开更多
膜结合型前列腺素E合成酶1(membrane-associated prostaglandin E synthase-1,mPGES-1)是前列腺素(prostaglandin,PG)E2生物合成过程中重要的终端限速酶,与环氧合酶2(cyclooxygenase-2,COX-2)功能性偶联参与机体多种生理及病理过程。近...膜结合型前列腺素E合成酶1(membrane-associated prostaglandin E synthase-1,mPGES-1)是前列腺素(prostaglandin,PG)E2生物合成过程中重要的终端限速酶,与环氧合酶2(cyclooxygenase-2,COX-2)功能性偶联参与机体多种生理及病理过程。近年来研究发现,mPGES-1在多种肿瘤组织中过度表达,与肿瘤的发生、发展密切相关。抑制mPGES-1的活性能有效降低PGE2的产生,同时能避免非甾体类抗炎药(non-steroidal anti-inflammatory drug,NSAID)及COX-2特异性抑制剂引起的心血管方面的不良反应,是一个比COX-2更理想、更安全的防治肿瘤的药物开发新靶点。本文就mPGES-1的分子生物学特征、与肿瘤发生和发展的相关性及其抑制剂的研究进展作一综述。展开更多
In order to analyze and explain the mechanism of the two small inhibitors （ADS-JI and ADS-J2） binding to HIV-1 gp41, a computational study is carried out to help identifying possible binding modes by docking these c...In order to analyze and explain the mechanism of the two small inhibitors （ADS-JI and ADS-J2） binding to HIV-1 gp41, a computational study is carried out to help identifying possible binding modes by docking these compounds onto the hydrophobic pocket on gp41 and characterize structures of binding complexes. The binding interactions of gp41-molecule and free energies of binding are obtained through molecular dynamics simulation and molecular mechanic/Poisson- Boitzmann surface area （ MM/PBSA ） calculation. Specific molecular interactions in the gp41-inhibitor complexes are identified. The present computational study complements the corresponding experimental investigation and helps establish a good starting point tbr further refinement of small molecular gp41 inhibitors.展开更多
With a view to finding out precisely how small peptides recognize a particular binding site of DNA, we have accomplished DNA binding studies of two peptides, H-Tyr-Arg-OH (YR) and H-Gly-Gly-His-OH (GGH) by using measu...With a view to finding out precisely how small peptides recognize a particular binding site of DNA, we have accomplished DNA binding studies of two peptides, H-Tyr-Arg-OH (YR) and H-Gly-Gly-His-OH (GGH) by using measurements in comparison with the binding between DNA and Hoechst 33258. The inhibition mode by YR and GGH to DNA binding of Hoechst 33258 was analyzed by Lineweaver-Burk plot which shows the plot of typical competitive inhibition at concentration of Hoechst 33258 from 3.66 ( 10-9 mol / L to 1.09 ( 10-8 mol / L. And it is concluded that YR binds to DNA in its minor groove (AT rich regions) with a binding constant K = 1.02 ( 108 (mol / L)-1. The GGH(s specificity is reduced at high concentration because it can also bind GC base pair.展开更多
文摘目的综述微管蛋白秋水仙碱结合位点抑制剂Combretastatin A-4(CA-4)类似物的研究进展。方法依据近期国内外公开发表的49篇文献,将CA-4类似物的研究进展分类、归纳并总结。结果微管蛋白秋水仙碱结合位点抑制剂(colchicine binding site inhibitors,CBSI)具有增殖抑制和血管破坏双重活性,近年来备受抗肿瘤药物研究人员的关注。CA-4类似物的抗肿瘤活性突出且结构简单,是CBSI中的重要组成部分。本文对CA-4类似物的结构特点及其构效关系进行了归纳总结。结论利用CA-4类似物的构效关系归纳总结进行开发新药已成为研究热点。
基金The National Basic Research Program of China (973 Program) (No. 2007CB936300)
文摘In order to analyze and explain the mechanism of the two small inhibitors （ADS-JI and ADS-J2） binding to HIV-1 gp41, a computational study is carried out to help identifying possible binding modes by docking these compounds onto the hydrophobic pocket on gp41 and characterize structures of binding complexes. The binding interactions of gp41-molecule and free energies of binding are obtained through molecular dynamics simulation and molecular mechanic/Poisson- Boitzmann surface area （ MM/PBSA ） calculation. Specific molecular interactions in the gp41-inhibitor complexes are identified. The present computational study complements the corresponding experimental investigation and helps establish a good starting point tbr further refinement of small molecular gp41 inhibitors.
文摘With a view to finding out precisely how small peptides recognize a particular binding site of DNA, we have accomplished DNA binding studies of two peptides, H-Tyr-Arg-OH (YR) and H-Gly-Gly-His-OH (GGH) by using measurements in comparison with the binding between DNA and Hoechst 33258. The inhibition mode by YR and GGH to DNA binding of Hoechst 33258 was analyzed by Lineweaver-Burk plot which shows the plot of typical competitive inhibition at concentration of Hoechst 33258 from 3.66 ( 10-9 mol / L to 1.09 ( 10-8 mol / L. And it is concluded that YR binds to DNA in its minor groove (AT rich regions) with a binding constant K = 1.02 ( 108 (mol / L)-1. The GGH(s specificity is reduced at high concentration because it can also bind GC base pair.
