Phosphorus-containing peptide analogs as peptidase inhibitors.
Phosphorus-containing peptide analogs as peptidase inhibitors.
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作为肽酶抑制剂的含磷肽类似物。
DOI：
10.1101/sqb.1987.052.01.012
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Hanson,JE
中科院分区：
文献类型：
--
作者：
Bartlett,PA;Marlowe,CK;Giannousis,PP;Hanson,JE
肽酶在生物体中发挥着各种作用，从消化的常规工作到高度特异性的激素调节。它们参与多种过程，如凝血和补体级联、血压调节、卵受精、蛋白质合成中的翻译后加工、肿瘤侵袭和退行性疾病如肺气肿和关节炎。合成的和天然存在的肽酶抑制剂已用于研究这些酶的功能和作为药剂。实际上，成功的高血压治疗包括使用肽酶抑制剂，该肽酶从其十肽前体产生八肽升压激素血管紧张素II，设计肽酶抑制剂的任务很简单，因为它们的机制相对较好地理解。所有已阐明其机制的肽酶都属于以下四类之一：丝氨酸和半胱氨酸肽酶，其反应通过共价酰基酶中间体进行，以及锌和天冬氨酸肽酶，其催化水直接加成到酰胺键。此外，抑制策略似乎在每一类肽酶中都是通用的。另一方面，这些机制和抑制策略的共性使得设计高特异性的低分子量抑制剂更具挑战性。
Peptidases play a variety of roles in living organisms, from the routine work of digestion to highly specific hormonal regulation. They are involved in such diverse processes as the blood-clotting and complement cascades, blood pressure regulation, ogg fertilization, posttranslational processing in protein synthesis, tumor invasion, and degenerative diseases such as emphysema and arthritis. Synthetic and naturally occurring peptidase inhibitors have been useful for studying the function of these enzymes and as medicinal agents. Indeed, a successful treatment for hypertension involves the use of an inhibitor of the peptidase that produces the octapeptide pressor hormone angiotensin II from its decapeptide precursor.The task of devising peptidase inhibitors is straightforward, since their mechanisms are relatively well understood. All peptidases whose mechanisms have been elucidated fall into one of four classes: the serine and cysteine peptidases, whose reactions proceed via a covalent acyl enzyme intermediate, and the zinc and aspattie peptidases, which catalyze the direct addition of water to the amide linkage. Moreover, inhibition strategies appear to be general within each class of peptidase. On the other hand, these generalities of mechanism and inhibition strategies make it more of a challenge to devise low-molecular-weight inhibitors of high specificity.