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

基本信息

批准号：
7749942
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
项目类别：
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/7749942
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 Depressed mood 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 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

项目摘要

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）：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）。已在来自加拿大树突甲虫 (DAFP) 的 AFP 中鉴定出增强剂，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。尽管已经鉴定出许多低分子量增强剂，并且其中一些确实在生理上增强DAFP的抗冻活性方面发挥作用，但增强剂的分子机制尚未得到很好的研究。 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（例如在冷冻食品中）至关重要。在这个项目中，我们将把所选柠檬酸盐衍生物的结构与理化性质联系起来。我们认为增强剂对 DAFP 抗冻活性的效率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理化性质而变化。为了揭示低分子量增强剂的分子机制，我们将探讨增强剂、DAFP 和冰之间可能的相互作用。由此可以开发识别和合理设计高效增强子的分子基础。该项目为 AFP 增强剂的机制研究提供了一种新方法。此外，AFP增强剂分子机制的描述将解决已发表的AFP机制之间的冲突。拟议的 AFP 和增强子研究对于增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公共健康，促进 AFP 和增强剂的潜在生物医学应用，例如移植器官的长期保存、冷冻保存和冷冻手术以及许多其他应用（例如冷冻食品）。