Johnson Sherida L, Jung Dawoon, Forino Martino, Chen Ya, Satterthwait Arnold, Rozanov Dmitry V, Strongin Alex Y, Pellecchia Maurizio
Cancer Research Center and Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
J Med Chem. 2006 Jan 12;49(1):27-30. doi: 10.1021/jm050892j.
We have recently identified a series of compounds that efficiently inhibit anthrax lethal factor (LF) metallo-protease. Here we present further structure-activity relationship and CoMFA (comparative molecular field analysis) studies on newly derived inhibitors. The obtained 3D QSAR model was subsequently compared with the X-ray structure of the complex between LF and a representative compound. Our studies form the basis for the rational design of additional compounds with improved activity and selectivity.
我们最近鉴定出了一系列能有效抑制炭疽致死因子(LF)金属蛋白酶的化合物。在此,我们展示了对新衍生抑制剂的进一步构效关系和比较分子场分析(CoMFA)研究。随后将所得的三维定量构效关系(3D QSAR)模型与LF和一种代表性化合物之间复合物的X射线结构进行了比较。我们的研究为合理设计活性和选择性更高的其他化合物奠定了基础。