Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA.
Molecules. 2012 Nov 30;17(12):14230-48. doi: 10.3390/molecules171214230.
The matrix metalloproteinases (MMPs) exhibit a broad array of activities, some catalytic and some non-catalytic in nature. An overall lack of selectivity has rendered small molecule, active site targeted MMP inhibitors problematic in execution. Inhibitors that favor few or individual members of the MMP family often take advantage of interactions outside the enzyme active site. We presently focus on peptide-based MMP inhibitors and probes that do not incorporate conventional Zn²⁺ binding groups. In some cases, these inhibitors and probes function by binding only secondary binding sites (exosites), while others bind both exosites and the active site. A myriad of MMP mediated-activities beyond selective catalysis can be inhibited by peptides, particularly cell adhesion, proliferation, motility, and invasion. Selective MMP binding peptides comprise highly customizable, unique imaging agents. Areas of needed improvement for MMP targeting peptides include binding affinity and stability.
基质金属蛋白酶（MMPs）具有广泛的活性，有些具有催化性质，有些则没有。由于缺乏整体选择性，小分子、活性位点靶向 MMP 抑制剂在执行过程中存在问题。那些有利于 MMP 家族中少数或个别成员的抑制剂通常利用酶活性位点之外的相互作用。我们目前专注于不包含传统 Zn²⁺结合基团的基于肽的 MMP 抑制剂和探针。在某些情况下，这些抑制剂和探针通过仅结合次要结合位点（外显子）起作用，而其他抑制剂和探针则同时结合外显子和活性位点。肽可以抑制除选择性催化以外的多种 MMP 介导的活性，特别是细胞黏附、增殖、迁移和侵袭。选择性 MMP 结合肽构成了高度可定制的独特成像剂。需要改进的 MMP 靶向肽的领域包括结合亲和力和稳定性。
