Protease inhibitors

Protease inhibitors (PI) are inorganic or also organic substances (mostly peptides) that inhibit the ubiquitously occurring proteases (protein-splitting hydrolases (newer name - peptidases that split proteins and peptides by hydrolytic splitting of the peptide bond) in their activities and thus prevent the degradation of certain proteins. Proteases (see enzymes below) have different substrate specificities depending on their type, some of them low (e.g. digestive enzymes), some of them very high (e.g. thrombin), and some of them have very high (e.g. thrombin) substrate specificities. Therefore, their inhibitory effect naturally leads to very different effects depending on the originally existing enzyme function (see below enzyme inhibitors).

In the living organism, the activities of proteases must naturally have a regulatory function in order to avoid excessive proteolytic processes (e.g. self-digestion in case of excess trypsin).

Thebody's own protease inhibitors serve to regulate the function of the body's own proteases (see enzyme inhibitors)

Vegetable protease inhibitors: Natural protease inhibitors are widely distributed in the plant kingdom mostly with specific effects on trypsin, chymotrypsin (peas, cereals, beans), plasmin (beans, peanuts) or thromboplastin (soybean). They can trigger both oral and inhalative allergies and are the cause of the frequent cross-reactions between minerals.

Various animal poisons (scorpion and snake venoms) contain protease inhibitors, which are partly responsible for their toxic effect.

Therapeutic protease inhibitors: Pharmaceutically manufactured protease inhibitors are used for various therapeutic purposes, e.g. to specifically inhibit peptidases of human pathogenic viruses or parasites.

For example, HIV protease inhibitors inhibit viral proteases (viral HIV-1 protease), which is essential for the replication of the virus. HCV protease inhibitors are used as antivirals for the treatment of HCV infections.

Furthermore, protease inhibitors have therapeutic effects in malaria (Lima AP et al. 2013), autoimmune diseases, neurodegenerative and tumor diseases (Eatemadi A et al. 2017). Thrombin inhibitors (e.g. melagatran and argatroban) influence blood coagulation and are used for the therapy or prevention of thrombosis. Inhibitors of the "angiotonin-converting-enzyme" - ACE - a zinc metalloprotease (-peptidase) also belong to the group of therapeutic protease inhibitors (antihypertensive).

1. Cameron-Vendrig A et al (2014) Antiatherothrombotic effects ofdipeptidyl peptidase inhibitors. Curr Atheroscler Rep 16:408.
2. Dunaevsky YE et al (2013) Fungal inhibitors of proteolytic enzymes: classification, properties, possible biological roles, and perspectives for practical use. Biochemistry 101:10-20.
3. Eatemadi A et al. (2017) Role of protease and protease inhibitors in cancer pathogenesis and treatment. Biomed Pharmacother 86:221-231.
4. Lima AP et al (2013) Cysteine peptidase inhibitors in trypanosomatide parasites. Curr Med Chem 20:3152-3173.
5. Rawlings ND et al (2004) Evolutionary families of peptidase inhibitors. Biochem J 378:705-716.
6. Yazbeck R et al (2009) Dipeptidyl peptidase inhibitors, an emerging drug class for inflammatory disease? Trends Pharmacol Sci 30:600-607.