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: 8448640
• 负责人: Xin Wen
• 金额: $ 10.49万
• 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/8448640
• 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）：已在许多生物体（例如鱼类、植物和昆虫）中鉴定出抗冻蛋白（AFP），使它们能够在低于冰点的温度下生存。它们的特点都是能够降低溶液的凝固点，而不会明显改变熔点，从而产生热滞后。昆虫 AFP 通常是最活跃的 AFP（比 I 型鱼类 AFP 活跃 10-100 倍）。许多 AFP 的抗冻活性在某些共溶质（称为增强剂）的存在下可以进一步增强。低分子量化学物质和大分子都已被确定为 AFP 的增强剂，并且一些增强剂确实在增强 AFP 的生理抗冻活性方面发挥作用。据报道，一些增强子可以特异性结合 AFP。然而，增强效应的机制仍然知之甚少。来自加拿大树突甲虫 (DAFP) 的 AFP 和增强子已被广泛研究。增强子与AFP的结合已被证明是增强子增强AFP抗冻活性的重要机制之一。不同AFP系统中的增强现象是否有共同的机制？在这个项目中，我们将研究一个重要的甲虫 AFP 系统，来自黄粉虫的黄粉虫 AFP (TmAFP) 和增强子。我们认为增强剂对 TmAFP 抗冻活性的增强效率取决于增强剂的理化性质。我们将评估选定的胺衍生物对 TmAFP 防冻活性的增强效率，并将其增强效率与其不同的物理化学性质相关联。我们将鉴定 TmAFP 和增强子之间可能的相互作用，并确定 TmAFP 中参与与增强子结合的关键氨基酸。 AFP 和增强剂的研究对于增进我们对生物系统的理解并促进高效 AFP 系统的实际生物医学应用的开发至关重要，例如在实验室低温下保存组织和人类健康以及其他工业应用，例如冷冻食品和水合物抑制。拟议的研究将深入了解 AFP 和 AFP 增强剂的分子机制，并解决有关 AFP 作用机制的相互矛盾的报告。