Nixon Andrew E, Wood Clive R
Dyax Corp, Cambridge, MA 02339, USA.
Curr Opin Drug Discov Devel. 2006 Mar;9(2):261-8.
The control of proteolysis in an organism is achieved under normal circumstances through a balance of protease production, degradation and inactivation, via interaction with an endogenous inhibitor. When one of these mechanisms for control of proteolysis fails, it can result in the onset or progression of disease. Control of aberrant proteolysis is, therefore, a potetntial point of therapeutic intervention, and can be achieved either through the replacement of an absent endogenous inhibitor or by dosing with an inhibitor that is specific for a protease that is being over produced. Engineered protein inhibitors of proteases offer the potential to overcome the difficulties involved in identifying specific inhibitors via small-molecule-based approaches.
在正常情况下，生物体中蛋白质水解的控制是通过蛋白酶的产生、降解和失活之间的平衡来实现的，这一过程通过与内源性抑制剂的相互作用来完成。当这些蛋白质水解控制机制中的任何一个失效时，就可能导致疾病的发生或进展。因此，控制异常的蛋白质水解是一个潜在的治疗干预点，可以通过补充缺失的内源性抑制剂或给予针对过度产生的蛋白酶的特异性抑制剂来实现。工程化的蛋白酶蛋白抑制剂有潜力克服通过基于小分子的方法鉴定特异性抑制剂所涉及的困难。
