Identification and Molecular Basis for Efficient Antifreeze Protein Enhancers

高效抗冻蛋白增强剂的鉴定和分子基础

• 批准号: 7558904
• 负责人: Xin Wen
• 金额: $ 10.84万
• 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 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7558904
• 关键词: Adsorption; Affinity; Antifreeze; Antifreeze Proteins; Appointment; Award; Binding; Biological; Biological Assay; Biomedical Research; Calorimetry; Canada; Carbon; Cations; Charge; Chemicals; Circular Dichroism; Citrates; Commit; Computer Simulation; Conflict (Psychology); Cryopreservation; Cryosurgery; Data; Development; Differential Scanning Calorimetry; Doctor of Philosophy; Educational Activities; Educational workshop; Enhancers; Exhibits; Faculty; Fish Type I APF; Fishes; Fluorescence Spectroscopy; Freezing; Frozen Foods; Funding; Future; Goals; Grant; Growth; Hydrogen Bonding; Hydrophobic Interactions; Ice; Insecta; Journals; Knowledge; Laboratories; Laboratory Research; Lead; Learning; Length; Letters; Ligands; Mainstreaming; Mentors; Mentorship; Methods; Minority; Molecular; Molecular Weight; Nature; Order Coleoptera; Organ Transplantation; Organism; Peer Review; Plants; Play; Postdoctoral Fellow; Procedures; Property; Protein Binding; Proteins; Public Health; Publications; Publishing; Recruitment Activity; Relative (related person); Research; Research Activity; Research Personnel; Role; Running; Salts; Scientist; Secure; Series; Solutions; Specificity; Staging; Structure; Students; Surface; Techniques; Temperature; Testing; Time; Titrations; Training; Underrepresented Minority; Universities; Work; Writing; base; biological systems; biophysical chemistry; career; depressed; design; electron donor; experience; improved; innovation; insight; interest; meetings; melting; novel; novel strategies; plasmid DNA; programs; protein expression; protein structure; research study; skills; teacher; tool

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). Enhancers have been identified in AFPs from the beetle Dendroides canadensis (DAFPs) to achieve the optimal antifreeze activity of DAFP. Citrate is the best enhancer that has been identified for DAFPs so far. Although many low molecular weight enhancers have been identified and some of them do play a role in enhancing the antifreeze activity of DAFPs physiologically, the molecular mechanism(s) of the enhancer(s) is not well developed. The study of AFPs and enhancers is essential to advance our understanding of the biological system and facilitate their potential biomedical applications, such as cryopreservation and cryosurgery, and many other applications (e.g., in frozen foods). In this project, we will correlate the structures with the physicochemical properties of selected citrate derivatives. We propose that the efficiency of enhancers on DAFP antifreeze activity depends on the physiochemical properties of the enhancers. We will characterize the enhancement efficiency of selected citrate derivatives on DAFP antifreeze activity and investigate how the enhancement efficiency of the systematically varied citrate derivatives varies with their differing physicochemical properties. To reveal the insights of the molecular mechanism of low molecular weight enhancers, we will then explore the possible interactions among the enhancers, DAFP, and ice. A molecular basis for identifying and rationally designing highly efficient enhancers can be thereby developed. This proposed project offers a new approach to the mechanistic study of AFP enhancers. In addition, the delineation of the molecular mechanism of AFP enhancers will resolve conflicts among published mechanisms of AFPs. The proposed study of AFPs and enhancers is essential to advance our understanding of the biological system. The results of the study will contribute to public health in facilitating the potential biomedical applications of AFPs and enhancers such as in longer storage of transplant organs, cryopreservation, and cryosurgery, and many other applications (e.g., in frozen foods).

描述（由申请人提供）：抗冻蛋白（AFP）已在许多生物体（如鱼类、植物和昆虫）中鉴定，使其能够在冰点以下的温度下存活。它们都具有降低溶液凝固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型鱼类AFP活跃10-100倍）。已经在来自甲虫加拿大石斛（Dendroides canadensis，DAFP）的AFP中鉴定了增强剂以实现DAFP的最佳抗冻活性。柠檬酸盐是迄今为止已确定的DAFP的最佳增强剂。尽管已经鉴定了许多低分子量增强剂，并且其中一些确实在生理上增强DAFP的抗冻活性中起作用，但是增强剂的分子机制还没有很好地开发。AFP和增强子的研究对于促进我们对生物系统的理解并促进其潜在的生物医学应用（例如冷冻保存和冷冻手术）以及许多其他应用（例如，冷冻食品）。在这个项目中，我们将关联的结构与选定的柠檬酸盐衍生物的物理化学性质。我们认为，增强剂对DAFP抗冻活性的影响取决于增强剂的理化性质。我们将表征所选柠檬酸盐衍生物对DAFP抗冻活性的增强效率，并研究系统变化的柠檬酸盐衍生物的增强效率如何随其不同的物理化学性质而变化。为了揭示低分子量增强剂的分子机制，我们将探索增强剂，DAFP和冰之间可能的相互作用。由此可以开发用于鉴定和合理设计高效增强子的分子基础。本研究为AFP增强剂的作用机制研究提供了一种新的途径。此外，阐明AFP增强子的分子机制将解决AFP已发表机制之间的冲突。对AFP和增强剂的拟议研究对于促进我们对生物系统的理解至关重要。该研究的结果将有助于促进AFP和增强剂的潜在生物医学应用，如移植器官的长期储存，冷冻保存和冷冻手术以及许多其他应用（例如，冷冻食品）。