Chiroptical Properties of Optically Active Thiazolidines Derived from Aldoses and Natural Mercapto-amino Acids

Optically active thiazolidines substituted at C(2) or/and C(4) show at least 2 Cotton effects below 260 nm, and different correlations between stereochemistry and CD hold for these compounds and their N-acyl derivatives. By such N-acylation all CD- -bands are enhanced, and the inherently chiral moiety -S-C- -N-C(=O)- of absolute conformation shown in Figure 4 always leads to a very strong negative Cotton effect near 205nm, regardless whether C(4) carries a C(=O)X group or not. Signs, positions, and magnitudes of the other CD bands are strongly influenced by other factors, too. Such a conformation is fixed in the lactones XXVIII through XXXIV, but is also preferred for 2,4-cis-disubstitution (with a polyhydroxyalkyl group at C(2) and a carboxylic group at C(4». Exciton interactions between the N-acyl and other (C=O)X - groups do not play a decisive role

Structure based inhibitor design targeting glycogen phosphorylase b. Virtual screening, synthesis, biochemical and biological assessment of novel N-acyl-β-d-glucopyranosylamines

Glycogen phosphorylase (GP) is a validated target for the development of new type 2 diabetes treatments. Exploiting the Zinc docking database, we report the in silico screening of 1888 β- D-glucopyranose-NH-CO-R putative GP inhibitors differing only in their R groups. CombiGlide and GOLD docking programs with different scoring functions were employed with the best performing methods combined in a “consensus scoring” approach to ranking of ligand binding affinities for the active site. Six selected candidates from the screening were then synthesized and their inhibitory potency was assessed both in vitro and ex vivo. Their inhibition constants’ values, in vitro, ranged from 5 to 377 µM while two of them were effective at causing inactivation of GP in rat hepatocytes at low µM concentrations. The crystal structures of GP in complex with the inhibitors were defined and provided the structural basis for their inhibitory potency and data for further structure based design of more potent inhibitors

Synthesis and in vivo studies of carbohydrate-based vaccines against group A Streptococcus

Carbohydrates, as carriers, providing numerous attachment points for the conjugation of peptide antigens and their optimal orientation for the recognition by cells of the immune system, reducing degradation of the attached peptide antigens and many other advantages make carbohydrate-based vaccine highly promising approach. Multiple copies of a single group A streptococcal (GAS) M protein derived specific peptide antigens (J8 or J14) were coupled onto carbohydrate cores (D-glucose and D-galactose) linked to lipophilic amino acids to produce a self-adjuvanting liposaccharide vaccine against GAS strains. In vivo experiments showed high serum IgG antibody titers against each of the incorporated peptide epitopes, J8 or J14