INTERNALLY QUENCHED FLUOROGENIC, ALPHA-HELICAL DIMERIC PEPTIDES AND GLYCOPEPTIDES FOR THE EVALUATION OF THE EFFECT OF GLYCOSYLATION ON THE CONFORMATION OF PEPTIDES

A panel of alpha-helical, dimeric coiled-coil peptides has been design ed and synthesized for the evaluation of the effect of glycosylation o n the conformation of these coiled-coil peptides, Two glycosylated bui lding blocks, 6-axido-6-deoxy-beta-D-glucopyranosyl)-L-threonine penta fluorophenyl ester 8 and lamino]-6-deoxy-beta-D-glucopyranosyl}-L-ther onine pentafluorophenyl ester 9 containing the fluorogenic 2-aminobenz amide (Abz) group, have been synthesized, These compounds have been ob tained by the glycosylation of N-alpha-Fmoc-Thr-OPfp with the correspo nding glycosyl trichloroacetimidate donors and have been incorporated into the solid-phase synthesis of the peptides 1-3 and 7 and glycopept ides 4-6, Compounds 1 and 4-7 have been synthesized as internally quen ched fluorogenic compounds where the Abz group has been employed as th e fluorogenic probe and 3-nitrotyrosine Tyr(NO2) as the quenching chro mophore. Steady-state fluorescence studies have provided evidence to s upport the dimerization of the a-helical peptides, Denaturation studie s, by fluorescence as well as CD spectroscopy, indicate that the intro duction of a carbohydrate moiety into the coiled-coil peptides has a s ignificant destabilizing effect on the alpha-helicity.