New directions in the synthesis of glycopeptide mimetics

For more than a decade, glycopeptides have attracted the attention of synth etic chemists as challenging targets for total chemical synthesis. Great st rides have been made, but the chemical synthesis of complex glycopeptides s till remains an arduous task. In recent years, discoveries at the forefront of biological research that have identified glycoproteins as key modulator s of cell - cell communication have created an urgent demand for quantities of homogeneous glycoconjugates for therapeutic and basic research applicat ions. In response, chemists have begun to explore various approaches to the construction of glycopeptide mimetics that have superior properties for th erapeutic applications, or lend themselves to a more facile synthesis. In t his Concepts article, we summarize contemporary approaches to the design of stable glycopeptide analogues, including C- and S-glycopeptides and glycop eptoids, as well as creative new strategies for generating glycopeptide mim ics with use of the chemoselective ligation technique.