Jiao Guan-Sheng, Cregar Lynne, Goldman Mark E, Millis Sherri Z, Tang Cho
Department of Chemistry, Hawaii Biotech Inc., 99-193 Aiea Heights Drive, Suite 200, Aiea, HI 96701, USA.
Bioorg Med Chem Lett. 2006 Mar 15;16(6):1527-31. doi: 10.1016/j.bmcl.2005.12.038. Epub 2006 Jan 4.
Anthrax lethal factor is a Zn(2+)-dependent metalloprotease and the key virulence factor of tripartite anthrax toxin secreted by Bacillus anthracis, the causative agent of anthrax. A series of guanidinylated 2,5-dideoxystreptamine derivatives were designed and synthesized as inhibitors of lethal factor, some of which show strong inhibitory activity against lethal factor in an in vitro FRET assay. Preparation and structure-activity relationships of these compounds are presented.
炭疽致死因子是一种依赖锌离子的金属蛋白酶,是炭疽病病原体炭疽芽孢杆菌分泌的三方炭疽毒素的关键毒力因子。设计并合成了一系列胍基化2,5-二脱氧链霉胺衍生物作为致死因子的抑制剂,其中一些在体外荧光共振能量转移测定中对致死因子表现出强抑制活性。本文介绍了这些化合物的制备及其构效关系。