"Bioorganic Chemistry - Carbohydrates, Peptides and Glycoconjugates."

在过去的几年中，冰重结晶的抑制剂在科学文献中占有突出地位，这是由于这些化合物的许多潜在的医学、商业和工业应用。这一高度集中的跨学科建议将继续我们在这一领域的努力。在过去的五年中，我们的实验室一直处于这一研究领域的最前沿，发现了两种新的C-连接的抗冻糖蛋白（C-AFGP）类似物，具有定制的抗冻活性，是冰重结晶的有效抑制剂。这些复杂的糖缀合物已被证明是有效的冷冻保护剂，能够在各种细胞系中使解冻后的细胞活力加倍。 虽然这是非常令人兴奋的，但迫切需要对这两类C-AFGP进行全面的结构-功能研究，以确定负责这种定制抗冻活性的结构部分。 为此，我们将继续在这方面的努力，重点是了解C-AFGP的一级结构，构象和配方调制冰重结晶。此外，我们将利用我们对C-AFGPs的研究所获得的知识，设计有效的冰重结晶小分子抑制剂。 将设计和合成几种不同类型的分子。 将使用热滞后和冰重结晶抑制的标准测定法评估所有化合物的抗冻蛋白比活性，并筛选任何潜在的冷冻保存能力。这些研究结果将有助于合理设计新的和改进的冷冻保护剂，并促进对生物材料冷冻保存过程中的冷冻损伤的理解。

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.