"Bioorganic Chemistry - Carbohydrates, Peptides and Glycoconjugates."

“生物有机化学 - 碳水化合物、肽和糖复合物。”

• 批准号: 283216-2012
• 负责人: Ben, Robert
• 金额: $ 2.55万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=548093
• 关键词: Bioorganic; Chemistry; Carbohydrates; Peptides; Glycoconjugates.

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.

在过去的几年里，冰重结晶的抑制剂在科学文献中占据了突出的地位，这是由于此类化合物在医疗、商业和工业方面的许多潜在应用。这项高度集中的跨学科提案将继续我们在这一领域的努力。在过去的五年里，我们的实验室一直处于这一研究领域的前沿，发现了两个新的C-连接抗冻糖蛋白(C-AFGP)类似物，它们具有定制的抗冻活性，是有效的冰重结晶抑制剂。这些复杂的糖偶联物已被证明是有效的冷冻保护剂，能够在各种细胞系中解冻后使细胞活力加倍。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，以确定这种定制的防冻活性的结构部分。为此，我们将继续在这一领域努力，重点了解C-AFGP的一级结构、构象和配方如何调控冰的再结晶。此外，我们还将利用从C-AFGP研究中获得的知识来设计有效的小分子冰重结晶抑制剂。将设计和合成几种不同类别的分子。将使用热滞后和抑制冰重结晶的标准分析来评估所有化合物的抗冻蛋白特定活性，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低温保护剂，并促进对生物材料低温保存过程中低温损伤的理解。