Carbohydrate peptidomimetics

Organski kemičari koriste metode kombinatorne kemije u kreiranju novih molekularnih građevnih elemenata s ciljem oponašanja strukture i svojstava njihovih prirodnih analoga. Korištenje peptida kao lijekova ograničeno je zbog (i) moguće proteolize u gastrointestinalnom traktu i krvnom serumu te (ii) gubitka nativne konformacije nakon modifikacije peptida. Rješenje predstavlja korištenje krutih, nepeptidnih kalupa koji nakon umetanja u peptid djeluju kao začetnici sekundarne strukture neophodne za njegovo vezivanje za receptor. Raznovrsnost ugljikohidrata u prirodi (anomerna stereokemija, veličina rigidnog prstena, moguća zaštita hidroksilnih skupina čime se utječe na polarnost) čini ih idealnim kandidatima za takve kalupe. Ugljikohidratni peptidomimetici pokazuju i veću otpornost prema proteolizi nego njihovi prirodni analozi.Organic chemists use combinatorial approach to create diverse molecular building blocks. The main objective in developing of such libraries is to mimic the structures and properties of natural products. The use of peptides as drugs is limited due to their low metabolic stability towards proteolysis and loss of its original conformation once truncated from the native protein. New combinatorial strategies involve the design of conformationally rigid nonpeptide scaffolds capable to induce specific secondary structures required for binding to the corresponding receptor upon inserting in the appropriate sites of the peptide. The great diversity of carbohydrates (anomeric stereochemistry, the rigid ring size, protection of hydroxylic groups that influence the polar character) makes themselves as ideal candidates. Compounds made of such building blocks are also more stable towards proteolysis in physiological systems