Swindell C S, Heerding J M, Krauss N E, Horwitz S B, Rao S, Ringel I
Department of Chemistry, Bryn Mawr College, Pennsylvania 19010.
J Med Chem. 1994 May 13;37(10):1446-9. doi: 10.1021/jm00036a009.
Taxol is a structurally novel and clinically effective antitumor drug, which, unlike other antimitotic agents, induces the assembly of tubulin into microtubules. To characterize the binding site(s) of taxol on the microtubule, taxol-based photoaffinity reagents 1 and 2 bearing photoreactive groups on the A-ring side chain were prepared and evaluated. Taxol analogue 1 exhibits better microtubule assembly activity, greater cytotoxicity toward J774.2 cells, and more specific and efficient photolabeling of the beta-subunit of tubulin than does analogue 2. Therefore, it would appear that 1 is the better candidate for further studies aimed at the characterization of the taxol binding site on the microtubule.
紫杉醇是一种结构新颖且临床有效的抗肿瘤药物，与其他抗有丝分裂剂不同，它能诱导微管蛋白组装成微管。为了表征紫杉醇在微管上的结合位点，制备并评估了在A环侧链带有光反应基团的基于紫杉醇的光亲和试剂1和2。紫杉醇类似物1比类似物2表现出更好的微管组装活性、对J774.2细胞更强的细胞毒性以及对微管蛋白β亚基更特异且高效的光标记。因此，对于旨在表征紫杉醇在微管上结合位点的进一步研究而言，1似乎是更好的候选物。
