[Prospects for the design of new therapeutically significant protease inhibitors based on knottins and sunflower seed trypsin inhibitor (SFTI 1)]
- PMID: 27562989
- DOI: 10.18097/PBMC20166204353
[Prospects for the design of new therapeutically significant protease inhibitors based on knottins and sunflower seed trypsin inhibitor (SFTI 1)]
Abstract
Plant seed knottins, mainly from the Cucurbitacea family, and sunflower seed trypsin inhibitor (SFTI 1) are the most low-molecular canonical peptide inhibitors of serine proteases. High efficiency of inhibition of various serine proteases, structure rigidity together with the possibility of limited variations of amino acid sequences, high chemical stability, lack of toxic properties, opportunity of production by either chemical synthesis or use of heterologous expression systems make these inhibitors attractive templates for design of new compounds for regulation of therapeutically significant serine protease activities. Hence the design of such compounds represents a prospective research field. The review considers structural characteristics of these inhibitors, their properties, methods of preparation and design of new analogs. Examples of successful employment of natural serine protease inhibitors belonging to knottin family and SFTI 1 as templates for the design of highly specific inhibitors of certain proteases are given.
Knottiny iz semian rasteniĭ, v osnovnom semeĭstva tykvennykh, i ingibitor tripsina iz semian podsolnechnika (SFTI 1) iavliaiutsia samymi nizkomolekuliarnymi kanonicheskimi peptidnymi ingibitorami serinovykh proteaz. Vysokaia éffektivnost' ingibirovaniia riada serinovykh proteaz, zhestkost' struktury pri vozmozhnosti ogranichennykh varitsiĭ aminokislotnoĭ posledovatel'nosti, vysokaia khimicheskaia stabil'nost', otsutstvie toksicheskikh svoĭstv, vozmozhnost' polucheniia khimicheskim sintezom i produktsii v sistemakh geterologicheskoĭ ékspressii delaiut ukazannye prirodnye ingibitory privlekatel'nym shablonom dlia dizaĭna novykh soedineniĭ – reguliatorov aktivnosteĭ terapevticheski znachimykh serinovykh proteaz, a razrabotku takikh soedineniĭ – perspektivnym napravleniem issledovaniĭ. V dannom obzore rassmotreny osobennosti struktury étikh ingibitorov, ikh svoĭstva, sposoby polucheniia i dizaĭna novykh analogov. Privedeny primery uspeshnogo ispol'zovaniia prirodnykh ingibitorov serinovykh proteaz semeĭstva knottinov i SFTI 1 v kachestve shablonov dlia dizaĭna vysokospetsifichnykh ingibitorov riada proteaz.
Keywords: design of peptide inhibitors of proteases; inhibitors; knottins; serine proteases.
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