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Design of Self-Assembling Triple Helices and Molecular Recognition of Collagen

胶原自组装三螺旋设计与分子识别

基本信息

批准号：
1709631
负责人：
Jeffrey Hartgerink
金额：
$ 52万
依托单位：
William Marsh Rice University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1709631&HistoricalAwards=false
关键词：
Design Self Assembling Triple Helices

项目摘要

In humans, collagen is the most abundant protein in the body and is found in nearly every tissue. Collagen has a huge array of functions from toughening our bones and giving strength to our skin to playing a key role in immunity. Collagen is constructed by a multistep sequence of self-assembly of the molecular components. Despite collagen's ubiquity and importance, the underlying structure, stability and mechanism of assembly are poorly understood. Prof. Hartgerink of Rice University conducts research to determine the rules of collagen stability and probe the assembly mechanisms. This fundamental knowledge could lead to a better understanding of diseases associated with collagen malfunction and also help with the design of next-generation biomaterials which mimic collagen. This research project provides the basis for interdisciplinary undergraduate and graduate education programs which combine chemical design with biology and medicine. High school science teachers are recruited to work with the Hartgerink group in the summer to develop exciting curriculum based on cutting edge research that can be directly translated to their high school chemistry and biology courses. These teachers later return with their entire science class for demonstrations and laboratory tours. Integration of this interdisciplinary research with secondary education science goals helps to inspire both the students as well as their teachers toward STEM related fields.There are two main goals in this project funded by the Macromolecular, Supramolecular and Nanochemistry Program of the National Science Foundation. The first goal is to expand our knowledge of pairwise amino acid interactions in the triple helix, the fundamental unit of collagen self-assembly. These pairwise interactions modulate the stability of triple helices as well as their self-assembly. Expanding this knowledge base is helping us to understand this important and extremely abundant protein family. In addition, it is providing new tools for chemists to design collagen based materials which are important for a wide variety of biomedical applications. The second goal is to describe a rational system for the specific molecular recognition of any member of the collagen family. These collagen targeting peptides (CTPs) use the pairwise interactions discovered above for sequence specific molecular recognition of a given collagen triple helix. CTPs work in highly complicated chemical environments such as a slice of tissue where hundreds of other competing molecules co-exist. The design of these CTPs should allow them to specifically target any natural extracellular matrix collagens, collagens found in the innate immune system or those found in bacteria and viruses.

在人类中，胶原蛋白是体内最丰富的蛋白质，几乎存在于每一种组织中。胶原蛋白具有一系列巨大的功能，从强化我们的骨骼和增强我们的皮肤到在免疫中发挥关键作用。胶原蛋白是通过分子组分的多步自组装序列构建的。尽管胶原蛋白的普遍性和重要性，基本的结构，稳定性和组装机制知之甚少。 Rice大学的Hartgerink教授进行研究，以确定胶原蛋白稳定性的规则并探索组装机制。这些基础知识可以更好地理解与胶原蛋白功能障碍相关的疾病，并有助于设计下一代模拟胶原蛋白的生物材料。该研究项目为跨学科的本科生和研究生教育课程提供了基础，这些课程将联合收割机化学设计与生物学和医学相结合。高中科学教师被招募与Hartgerink集团在夏季开发基于前沿研究，可以直接转化为他们的高中化学和生物课程令人兴奋的课程。这些教师随后带着他们整个科学班的学生回来进行演示和实验室图尔斯参观。这项跨学科研究与中学教育科学目标的整合有助于激发学生和教师对STEM相关领域的兴趣。该项目由美国国家科学基金会的大分子，超分子和纳米化学计划资助，主要有两个目标。第一个目标是扩大我们的知识，成对的氨基酸相互作用的三螺旋，胶原蛋白自组装的基本单位。这些成对的相互作用调节三螺旋的稳定性以及它们的自组装。扩展这一知识基础有助于我们了解这个重要且极其丰富的蛋白质家族。此外，它还为化学家设计胶原基材料提供了新的工具，这些材料对各种生物医学应用都很重要。第二个目标是描述一个合理的系统，用于胶原蛋白家族任何成员的特异性分子识别。这些胶原靶向肽（CTP）使用上文发现的成对相互作用用于给定胶原三螺旋的序列特异性分子识别。CTP在高度复杂的化学环境中工作，例如一片组织，其中数百种其他竞争分子共存。这些CTP的设计应允许它们特异性靶向任何天然细胞外基质胶原蛋白、先天免疫系统中发现的胶原蛋白或细菌和病毒中发现的胶原蛋白。