| Iminosugars are mimics of carbohydrates and are effective inhibitors of their processing enzymes, binding reversibly and competitively to glycosidases. Libraries of N-alkyl piperidine and N-alkyl-C1-gem-dialkyl pyrrolidine iminosugars were synthesized. These inhibitors were found to improve antiviral activity against bovine viral diarrhea virus (BVDV) and Dengue virus. In both antiviral studies (N-alkyl piperidines and N-alkyl-C1-gem-dialkyl pyrrolidines), the extension of an alkyl chain provides for a very hydrophobic substrate and actually increased potency of the antiviral. Previous research had indicated that chains past nine carbons had increased cytotoxicity, and decreased alpha-glycosidase I/antiviral activity. However, our results open the pathway toward inhibitor structures that likely inhibit resident beta-glycosidase, glucoceramidase.;Additionally, hyaluronic acid and chondroitin sulfate (being important extracellular matrix constituents and natural glycosidase substrates) were chemically modified to develop hydrogel material. Mixed polyethylene glycol/glycosaminoglycan gels were fabricated using a metal-free, 3+2 cycloaddition reaction. Further, a novel visible-light initiated photo-polymerization system was developed. Acrylated glycosaminoglycan derivatives were synthesized via conjugation with the metal-free, 3+2 cycloaddition technique and hydrogels were formed utilizing our low-intensity visible light photo-reaction. These gels were successfully cross-linked, swollen, and are being studied for their potential value biomedical engineering. |
