کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1376364 | 981956 | 2008 | 6 صفحه PDF | دانلود رایگان |

Recently, we identified a thiocarbazate that exhibits potent inhibitory activity against human cathepsin L. Since this structure represents a novel chemotype with potential for activity against the entire cysteine protease family, we designed, synthesized, and assayed a series of analogs to probe the mechanism of action, as well as the structural requirements for cathepsin L activity. Molecular docking studies using coordinates of a papain–inhibitor complex as a model for cathepsin L provided useful insights.
A novel series of thiocarbazates was designed and synthesized to probe the structural requirements for cathepsin L inhibitory activity. These studies were guided by molecular docking studies using coordinates of a papain–inhibitor complex as a model for cathepsin L, and led to an understanding of the specific binding interactions as well as appropriate carbonyl reactivity required for potent activity. Furthermore, a highly potent inhibitor of cathepsin L (IC50 7 nM) was identified a result of these studies.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 12, 15 June 2008, Pages 3646–3651