From the Proteolysis Laboratory, Molecular Biology Institute of Barcelona (Consejo Superior de Investigaciones Científicas), Barcelona Science Park, Baldiri Reixac 15-21, 08028 Barcelona, Catalonia, Spain
J Biol Chem. 2017 Oct 27;292(43):17975-17976. doi: 10.1074/jbc.H117.806075.
Drug candidates against matrix metalloproteinases (MMPs) failed in the clinic in the past because their strong zinc-targeting warheads led to a lack of specificity. More recently, significant selectivity among MMPs was achieved by blocking the enzymes' specificity pockets, nearby exosites, and downstream domains. Scannevin and colleagues now elegantly twist the plot and achieve ultimate selectivity: They target MMP-9 by allosterically preventing activation of its zymogen.
过去，针对基质金属蛋白酶（MMPs）的药物候选物在临床上失败了，因为它们强烈的锌靶向弹头导致缺乏特异性。最近，通过阻断酶的特异性口袋、附近的外位和下游结构域，在 MMPs 中实现了显著的选择性。Scannevin 及其同事现在巧妙地扭转了局面，实现了最终的选择性：他们通过别构抑制其酶原的激活来靶向 MMP-9。
