Phosphoramidate-based peptidomimetic inhibitors of membrane type-1 matrix metalloproteinase.
Phosphoramidate-based peptidomimetic inhibitors of membrane type-1 matrix metalloproteinase.
复制标题
膜1型基质金属蛋白酶的基于磷酰胺的肽型抑制剂。
DOI：
10.3109/14756366.2015.1010528
复制
发表时间：
2016
影响因子：
5.6
通讯作者：
Berkman CE
中科院分区：
文献类型：
--
作者：
Mendes DE;Wong-On-Wing A;Berkman CE
Membrane-type I matrix metalloproteinases (MT1-MMP) is an enzyme critical to the remodeling and homeostasis of extracellular matrix, and when over expressed it contributes to metastasis and cancer cell progression. Because of its role and implication as a biomarker that is upregulated in various cancers, MT1-MMP has become an attractive target for drug discovery. A small pilot library of peptidomimetics containing a phosphoramidate core as a zinc-binding group was synthesized and tested for inhibitory potency against MT1-MMP. From this library, a novel two residue peptidomimetic scaffold was identified that confers potency against MT1-MMP at submicromolar concentrations. The results of this study confirm that for this scaffold, valine is favored as a P1 residue and leucine in the P1′ position. Furthermore, steric tolerance was observed for the N-terminus, thus implicating that a second-generation library could be constructed to extend the scaffold to P2 without concomitant loss of affinity within the MT1-MMP catalytic domain.
