"Bioorganic Chemistry - Carbohydrates, Peptides and Glycoconjugates."

“生物有机化学 - 碳水化合物、肽和糖复合物。”

基本信息

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：
2016
资助国家：
加拿大
起止时间：
2016-01-01 至 2017-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=594796
关键词：
Bioorganic Chemistry Carbohydrates Peptides Glycoconjugates.

项目摘要

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.

在过去的几年中，冰结晶的抑制剂在科学文献中显着地认为，这是由于这种化合物的许多潜在医疗，商业和工业应用所致。这项高度关注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该研究领域的最前沿，发现两种新型的C链接抗冻糖蛋白（C-AFGP）类似物具有具有定制的抗冻冻活性，并且是对冰结晶的有效抑制剂。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透射后的细胞活力加倍。尽管这是非常令人兴奋的，迫切需要对这两类C-AFGP的结构功能研究，以确定负责这种定制的防冻活动的结构性部分。为此，我们将继续在这一领域的努力，重点是了解C-AFGP的主要结构，构象和配方如何调节冰的重结晶。此外，我们将使用从C-AFGP的研究中获得的知识来设计有效的冰重结晶的小分子抑制剂。将设计和合成几种不同类别的分子。所有化合物将使用标准测定法对抗冻蛋白特异性活性进行评估，用于热滞后和抑制冰重结晶，并筛选出任何潜在的冷冻保存能力。这些研究的结果将促进新的和改进的冷冻保护剂的合理设计，并在生物材料的冷冻保存过程中促进对冷冻机的理解。