Structure-Based Optimization of a Peptidyl Inhibitor against Calcineurin-Nuclear Factor of Activated T Cell (NFAT) Interaction
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- 作者：Ziqing Qian ; Patrick G. Dougherty ; Tao Liu ; Shameema Oottikkal ; Patrick G. Hogan ; Christopher M. Hadad ; Dehua Pei
- 刊名：Journal of Medicinal Chemistry
- 出版年：2014
- 出版时间：September 25, 2014
- 年：2014
- 卷：57
- 期：18
- 页码：7792-7797
- 全文大小：324K
- ISSN：1520-4804
文摘
Calcineurin inhibitors such as cyclosporine A and FK506 are effective immunosuppressants but produce severe side effects. Rational modification of a previously reported peptide inhibitor, GPHPVIVITGPHEE (KD 鈭?500 nM), by replacing the two valine residues with tert-leucine and the C-terminal proline with a cis-proline analogue, gave an improved inhibitor ZIZIT-cisPro, which binds to calcineurin with a KD value of 2.6 nM and is more resistant to proteolysis.