X射线、核磁共振及分子建模在基质金属蛋白酶抑制剂设计中的应用。

The application of x-ray, NMR, and molecular modeling in the design of MMP inhibitors.

作者信息

Rush Thomas S, Powers Robert

机构信息

Structural Biology & Computational Chemistry, Department of Chemical & Screening Sciences, Wyeth Research, 87 Cambridge Park Dr. Cambridge, MA, 02140, USA.

出版信息

Curr Top Med Chem. 2004;4(12):1311-27. doi: 10.2174/1568026043387999.

DOI:10.2174/1568026043387999

PMID:15320728

Abstract

The following review discusses the successful application of X-ray, NMR, and molecular modeling in the design of potent and selective inhibitors of matrix metalloproteinases (MMPs) and TNFalpha-converting enzyme (TACE) from Wyeth. The importance of protein and ligand mobility as it impacts structure-based design is also discussed. The MMPs are an active target for a variety of diseases, including cancer and arthritis.

摘要

以下综述讨论了X射线、核磁共振（NMR）以及分子建模在辉瑞公司设计基质金属蛋白酶（MMPs）和肿瘤坏死因子α转换酶（TACE）强效选择性抑制剂方面的成功应用。还讨论了蛋白质和配体流动性对基于结构的药物设计的影响。MMPs是包括癌症和关节炎在内的多种疾病的有效靶点。