IDENTIFICATION AND MOLECULAR BASIS FOR EFFICIENT ANTIFREEZE PROTIEN ENHANCERS

高效抗冻蛋白增强剂的鉴定和分子基础

• 批准号: 8625766
• 负责人: Xin Wen
• 金额: $ 10.88万
• 依托单位: CALIFORNIA STATE UNIVERSITY LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8625766
• 关键词: Adsorption; Affect; Affinity; Amines; Amino Acids; Antifreeze; Antifreeze Proteins; Binding; Biological Assay; Chemicals; Circular Dichroism Spectroscopy; Conflict (Psychology); Cryopreservation; Cryosurgery; Data; Depressed mood; Development; Enhancers; Exhibits; Fish Type I APF; Fishes; Food Preservation; Freezing; Frozen Foods; Funding; Goals; Health; Heterocyclic Compounds; Human; Hydrogen; Hydrogen Bonding; Hydrophobic Interactions; Ice; Insecta; Knowledge; Measures; Methods; Modification; Molecular; NMR Spectroscopy; Nature; Nitrogen; Order Coleoptera; Organism; Plants; Play; Property; Public Health; Reporting; Research; Role; Series; Site-Directed Mutagenesis; Solutions; Structure; Surface; System; Temperature; Tenebrio; Time; Tissue Preservation; Variant; Water; Work; base; biological systems; cold temperature; electron donor; improved; insight; macromolecule; melting; molecular mass; practical application; solute

DESCRIPTION (provided by applicant): Antifreeze proteins (AFPs) have been identified in a number of organisms, such as fish, plants, and insects, to allow them to survive at subfreezing temperatures. They are all characterized by their ability to depress the freezing point of the solution without appreciably altering the melting point thereby producing a thermal hysteresis. Insect AFPs are often the most active AFPs (10-100 times more active than type I fish AFPs). The antifreeze activities of many AFPs can be further enhanced in the presence of certain co-solutes (called enhancers). Both low molecular mass chemicals and macromolecules have been identified as enhancers for AFPs and some of the enhancers do play a role in enhancing the antifreeze activity of AFPs physiologically. Some of the enhancers have been reported to bind AFPs specifically. The mechanism of the enhancement effect, however, is still poorly described. The AFP from the beetle Dendroides canadensis (DAFP) and the enhancers have been extensively studied. The binding of enhancers to AFP has been demonstrated as one important mechanism for the enhancement effect of enhancers on the antifreeze activity of AFPs. Is there a common mechanism for the enhancement phenomena in different AFP systems? In this project, we will examine an important beetle AFP system, a mealworm AFP from Tenebrio molitor (TmAFP) and the enhancers. We propose that the enhancement efficiency of the enhancers for TmAFP antifreeze activity depends on the physiochemical properties of the enhancers. We will assess the enhancement efficiency of selected amine derivatives on TmAFP antifreeze activity and correlate their enhancement efficiency with their differing physicochemical properties. We will identify the possible interactions between TmAFP and the enhancers and determine the key amino acids in TmAFP involving in binding to the enhancers. The study of AFPs and enhancers is essential to advance our understanding of the biological system and facilitate the development of highly efficient AFP systems for their practical biomedical applications, such as in preservation of tissues at low temperatures in the lab and in human health as well as other industrial applications, such as in frozen foods and in hydrate inhibition. The proposed research will provide insights into the molecular mechanism of AFP and AFP enhancers and resolve conflicting reports regarding the mechanism of action of AFPs.

描述（由申请人提供）：在许多生物（例如鱼类，植物和昆虫）中鉴定出抗冻蛋白（AFP），以使其在亚冻结温度下生存。它们的特征都是它们能够降低溶液的冰点而不明显改变熔点从而产生​​热滞后的能力。昆虫AFP通常是最活跃的AFP（比I型鱼AFP高10-100倍）。在存在某些共糖（称为增强剂）的情况下，可以进一步增强许多AFP的防冻活性。低分子质量化学物质和大分子都被确定为AFP的增强剂，一些增强剂确实在增强AFPS生理上的抗冻活性方面发挥了作用。据报道，某些增强剂特别结合了AFP。然而，增强效应的机制仍然很差。甲虫Dendroides Canadensis（DAFP）和增强剂的AFP已经进行了广泛的研究。增强子与AFP的结合已被证明是增强子对AFPS抗冻活性增强作用的重要机制。在不同的AFP系统中是否有增强现象的共同机制？在这个项目中，我们将检查一个重要的甲虫AFP系统，Tenebrio Molitor（TMAFP）的粉虫AFP和增强剂。我们建议增强子对TMAFP抗冻活性的增强效率取决于增强子的生理特性。我们将评估所选胺衍生物对TMAFP抗冻活性的增强效率，并将其增强效率与它们不同的理化特性相关联。我们将确定TMAFP与增强剂之间的可能相互作用，并确定涉及与增强剂结合的TMAFP中的关键氨基酸。对AFP和增强剂的研究对于提高我们对生物系统的理解至关重要，并促进了用于实用生物医学应用的高效AFP系统的开发，例如在实验室，人类健康以及其他工业应用以及在冷冻食品和水合抑制中保存组织的组织。拟议的研究将为AFP和AFP增强剂的分子机制提供见解，并解决有关AFP的作用机理的相互矛盾的报告。