"Bioorganic Chemistry - Carbohydrates, Peptides and Glycoconjugates."

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During the last several years, inhibitors of ice recrystallization have figured prominently in the scientific literature and this is due to the many potential medical, commercial and industrial applications of such compounds. This highly focussed interdisciplinary proposal will continue our efforts in this area. During the past five years our laboratory has been at the forefront of this research area with the discovery of two novel C-linked antifreeze glycoprotein (C-AFGP) analogues that possess custom-tailored antifreeze activity and are potent inhibitors of ice recrystallization. These complex glyconconjugates have proven to be effective cryoprotectants capable of doubling cell viability post-thaw in various cell lines. While this is very exciting, comprehensive structure-function studies on these two classes of C-AFGPs are urgently required to identify the structural moieties responsible for this custom-tailored antifreeze activity. Towards this end, we will continue our efforts in this area with emphasis on understanding how C-AFGP primary structure, conformation and formulation modulate ice recrystallization. In addition, we will design potent small molecule inhibitors of ice recrystallization using the knowledge gained from our studies on C-AFGPs. Several different classes of molecules will be designed and synthesized. All compounds will be assessed for antifreeze protein-specific activity using standard assays for thermal hysteresis and inhibition of ice recrystallization and screened for any potential cryopreservation ability. The results from these studies will facilitate the rational design of new and improved cryoprotectants and advance the understanding of cryoinjury during cryopreservation of biological materials.