抗肿瘤药物克氏菌素的选择性蛋白水解活性。

Zein N, Casazza A M, Doyle T W, Leet J E, Schroeder D R, Solomon W, Nadler S G

Bristol-Myers Squibb, Pharmaceutical Research Institute, Princeton, NJ 08543-4000.

Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8009-12. doi: 10.1073/pnas.90.17.8009.

Kedarcidin is a potent antitumor antibiotic chromoprotein, composed of an enediyne-containing chromophore embedded in a highly acidic single chain polypeptide. The chromophore was shown to cleave duplex DNA site-specifically in a single-stranded manner. Herein, we report that in vitro, the kedarcidin apoprotein, which lacks any detectable chromophore, cleaves proteins selectively. Histones that are the most opposite in net charge to the apoprotein are cleaved most readily. Our findings imply that the potency of kedarcidin results from the combination of a DNA damaging-chromophore and a protease-like apoprotein.

凯德菌素是一种强效抗肿瘤抗生素色蛋白，由嵌入高度酸性单链多肽中的含烯二炔发色团组成。该发色团被证明能以单链方式位点特异性切割双链DNA。在此，我们报告在体外，缺乏任何可检测发色团的凯德菌素脱辅基蛋白能选择性切割蛋白质。与脱辅基蛋白净电荷差异最大的组蛋白最容易被切割。我们的研究结果表明，凯德菌素的效力源于DNA损伤发色团和蛋白酶样脱辅基蛋白的结合。