Peptidomimetics

Podložnost proteolitičkim enzimima, polarnost koja otežava transport kroz lipidni dvosloj te prevelika konformacijska sloboda ograničavaju terapeutsku primjenu peptida. Primjenom njihovih mimetika moguće je prevladati spomenute nedostatke, tako da dizajn i sinteza peptidomimetika predstavljaju moćno oruđe za pripravu lijekova koji djeluju kao inhibitori enzima ili ligandi za različite receptore. Dizajn peptidomimetika bazira se na: (i) zamjeni dijela peptidne okosnice nepeptidnim fragmentom, (ii) modifikaciji bočnih ogranaka i(li) (iii) ograničavanju konformacijske slobode, s ciljem oponašanja onog fragmenta peptidne sekundarne strukture koji je odgovoran za molekulsko prepoznavanje. Na taj se način oponaša biološka aktivnost prirodnih peptida, a moguće je ostvariti i poboljšanu selektivnost, efikasnost, biodostupnost i produljenu biološku aktivnost.The low metabolic stability towards proteolytic enzymes, polar character that disables their transport through lipide bilayer as well as the conformational freedom limit their therapeutic application. Since those adversities might be prevailed by using of their mimetics, peptidomimetic design and synthesis present a powerfull tools for the preparation of drugs acting as enzyme inhibitors or receptor ligands. The design of peptidomimetics is based on: (i) the replacement of the peptide backbone with non-peptide fragment, (ii) the modification of the side-chains and/or (iii) the locking the conformational freedom in order to mimic secondary structure element responsible for molecular recognition. This approach not only enables the mimicking of the biological activity, but also improve selectivity, efficiency, bioavailability and activity