2′-Linking of Lipids and Other Functions to Uridine through 1,2,3-Triazoles and Membrane Anchoring of the Amphiphilic Products

A straightforward synthesis of 2'-functionalized uridines was developed based on a Cu-catalyzed cycloaddition of 2'-azido-2'-deoxyuridine and functionalized alkynes. The functions comprise biochemically important groups such as lipids, a fluorescent marker (Cy5 analogue), pentaacetylglucose, lysine and biotin, and are linked to the 2'-position of uridine by a 1,2,3-triazole ring. A number of NMR spectroscopic investigations revealed that the lipidated 2'-triazolyl-2'-deoxyuridines anchor themselves in the phospholipid membranes without affecting the molecular order in the double layers; the polar moieties - uracil, ribose and triazole - are located in the lipid/water interface of the membrane.