Shamsi Tooba Naz, Parveen Romana, Fatima Sadaf
Genes and Proteins Lab., Department of Biotechnology, Jamia Millia Islamia, New Delhi 110025, India.
Genes and Proteins Lab., Department of Biotechnology, Jamia Millia Islamia, New Delhi 110025, India.
Int J Biol Macromol. 2016 Oct;91:1120-33. doi: 10.1016/j.ijbiomac.2016.02.069. Epub 2016 Mar 5.
This review describes Protease Inhibitors (PIs) which target or inhibit proteases, protein digesting enzymes. These proteases play a crucial task in many biological events including digestion, blood coagulation, apoptosis etc. Regardless of their crucial roles, they need to be checked regularly by PIs as their excess may possibly damage host organism. On basis of amino acid composition of PIs where Protease-PI enzymatic reactions occur i.e. serine, cysteine, and aspartic acid, they are classified. Nowadays, various PIs are being worked upon to fight various parasitic or viral diseases including malaria, schistosomiasis, colds, flu', dengue etc. They prevent an ongoing process begun by carcinogen exposure by keeping a check on metastasis. They also possess potential to reduce carcinogen-induced, increased levels of gene amplification to almost normal levels. Some PIs can principally be used for treatment of hypertension and congestive heart failure by blocking conversion of angiotensin I to angiotensin II for example Angiotensin-converting enzyme inhibitors (ACEIs). Also PIs target amyloid β-peptide (Aβ) level in brain which is prime responsible for development of Alzheimer's Disease (AD). Also, PIs inhibit enzymatic activity of HIV-1 Protease Receptor (PR) by preventing cleavage events in Gag and Gag-Pol that result in production of non-virulent virus particles.
本综述介绍了靶向或抑制蛋白酶(即蛋白质消化酶)的蛋白酶抑制剂(PIs)。这些蛋白酶在包括消化、血液凝固、细胞凋亡等许多生物学过程中发挥着关键作用。尽管它们起着至关重要的作用,但由于其过量可能会损害宿主生物体,因此需要蛋白酶抑制剂对其进行定期检查。根据蛋白酶 - 蛋白酶抑制剂酶促反应发生的氨基酸组成,即丝氨酸、半胱氨酸和天冬氨酸,对它们进行分类。如今,人们正在研究各种蛋白酶抑制剂来对抗各种寄生虫或病毒性疾病,包括疟疾、血吸虫病、感冒、流感、登革热等。它们通过控制转移来阻止由致癌物暴露引发的正在进行的过程。它们还具有将致癌物诱导的基因扩增水平升高降低至几乎正常水平的潜力。例如,一些蛋白酶抑制剂主要可用于治疗高血压和充血性心力衰竭,通过阻断血管紧张素I向血管紧张素II的转化,即血管紧张素转换酶抑制剂(ACEIs)。此外,蛋白酶抑制剂还可靶向大脑中的淀粉样β肽(Aβ)水平,而淀粉样β肽是导致阿尔茨海默病(AD)的主要原因。此外,蛋白酶抑制剂通过阻止Gag和Gag - Pol中的切割事件来抑制HIV - 1蛋白酶受体(PR)的酶活性,这些切割事件会导致产生无毒性的病毒颗粒。