Potent Inhibitors of β-Tryptase and Human Leukocyte Elastase Based on the MCoTI-II Scaffold
Potent Inhibitors of β-Tryptase and Human Leukocyte Elastase Based on the MCoTI-II Scaffold
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DOI：
10.1021/jm901233u
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发表时间：
2009-10-22
影响因子：
7.3
通讯作者：
Tate, Edward W.
中科院分区：
文献类型：
--
作者：
Thongyoo, Panumart;Bonomelli, Camille;Tate, Edward W.
MCoTI-II是一类称为环肽的微蛋白的成员，其具有赋予特殊生理稳定性和结构刚性的大环内酰胺-胱氨酸结支架。活性环中残基的修饰和工程化截短导致MCoTI-II类似物对两种治疗上重要的丝氨酸蛋白酶具有有效活性：β-类胰蛋白酶和人白细胞弹性蛋白酶。这些结果表明，MCoTI-II是开发针对炎症性疾病靶点的蛋白酶抑制剂的通用支架。
MCoTI-lI is a member of a class of microproteins known as cyclotides that possess a macrolactam-cystine knot scaffold imparting exceptional physiological stability and structural rigidity. Modification of residues in the active loop and engineered truncations have resulted in MCoTI-II analogues that possess potent activity against two therapeutically significant serine proteases: beta-tryptase and human leukocyte elastase. These results suggest that MCoTI-II is a versatile scaffold for the development of protease inhibitors against targets in inflammatory disease.