Peptidomimetics as drugs

Tijekom posljednja tri desetljeća otkriven je i karakteriziran veliki broj biološki aktivnih peptida koji, zahvaljujući interakcijama s membranskim receptorima, kontroliraju različite vitalne funkcije. Unatoč golemom biološkom potencijalu, njihova je terapeutska primjena limitirana (i) podložnošću proteolitičkim enzimima, (ii) polarnošću koja otežava transport kroz lipidni dvosloj te (iii) prevelikom konformacijskom slobodom koja im dopušta zauzimanje različitih 3D-struktura i vezivanje s neželjenim receptorima. Takva se nepovoljna svojstva prirodnih peptida uspješno prevladavaju primjenom njihovih mimetika. Riječ je o peptidnim ili nepeptidnim strukturama koje oponašaju onaj element peptidne sekundarne strukture odgovoran za molekulsko prepoznavanje, odnosno oponašaju biološku aktivnost prirodnih peptida. Osim poboljšane selektivnosti i efikasnosti, peptidomimetike karakterizira i povećana biodostupnost i produljena biološka aktivnost.During the last three decades a numerous biologically active peptides have been discovered and characterized. Owing to the interaction with their membrane-bound receptors, these bioactive peptides control a series of vital functions. Despite their enormous biological potential, the use of peptides as therapeutics is limited due to (i) low metabolic stability towards proteolytic enzymes, (ii) polar character that disables their transport through lipide bilayer and (iii) conformational freedom that allows the formation of numerous 3D-structures enabled to react with various undesired receptors. Those adversities might be prevailed by using of peptidomimetics. A peptidomimetic compound may be defined as a peptide or non-peptide substance mimicking a secondary structure of the native peptide responsible for molecular recognition and biological activity. Apart from being much more selective and efficient than native peptides, peptidomimetics show greater oral bioavailability and the biological activity is prolonged