Designing sequential functionality into polypeptide side-chains to mimic complex biopolymers

许多海洋生物具有丰富的粘附能力，这是众所周知的。每年，全世界都要花费大量的时间和金钱，从被污染的船只和其他暴露在海洋中的人造建筑物上清除藤壶。许多永久附着的海洋生物所产生的黏附蛋白是非凡的，因为它们可以在很宽的温度范围、波动的盐度、湿度以及海洋环境中的潮汐、波浪和水流中发挥作用。相比之下，人造粘合剂在潮湿环境中的成功需要仔细清洁表面，通常还必须进行化学处理和/或部分干燥。海洋胶粘剂也被用于外科手术和牙科的组织胶，但它们生产成本昂贵，并可能引起免疫反应。该项目将开发海洋粘合剂的简化模拟，以确定设计和合成适用于潮湿环境的优质粘合剂所需的关键成分和工艺。本提案中开发的概念有潜力进一步用于制备可降解的合成多肽材料，用于下游湿粘附应用，如医学和牙科等领域。这笔资金还将用于招募和培训化学和材料研究领域的女性和代表性不足的少数民族学生，为STEM劳动力做出巨大贡献。摘要在过去的几十年里，贻贝胶黏剂中关键聚合物组分蛋白质的性能和复杂性受到了广泛的关注。除了大量的努力来研究和破译生物过程，也有很多努力复制贻贝黏附蛋白（MAPs）使用合成聚合物。与生物来源的蛋白质相比，用于湿粘合剂应用的合成聚合物具有潜在的优势，包括低成本的可扩展生产，没有生物污染物，在某些情况下，可以改善医学或工业应用的性能。这些聚合物主要集中在模仿贻贝蛋白质的3,4-去羟基苯基- l-丙氨酸含量，但很少关注map的许多其他官能团和特征，如疏水性和带电基团，以及由溶液pH和氧化还原电位的变化引起的物理和化学变化。尽管已经有人尝试模仿合成聚合物中的大部分（如果不是全部的话）这些特征，但这仍然是一个具有挑战性的问题，特别是在保留氨基酸序列信息和组成均匀性方面。在这个项目中，提出了一种新的方法来解决这一挑战，通过使用附着在具有额外仿生功能的均多肽支架上的均匀侧链肽序列来模拟MAP序列信息。提出的研究旨在提高合成聚合物的功能复杂程度，更接近于真正模仿多功能蛋白质的复杂性。从这些研究中获得的知识也将产生可扩展的合成方法和设计规则，可应用于模仿其他序列特异性蛋白质材料。该提案中的外展目标将继续PI在以前nsf资助的更广泛影响中开发的当前努力，为女性和代表性不足的少数民族学生准备STEM劳动力。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Non-Technical AbstractThe prolific adhesive capabilities of many marine organisms are well known. Each year a considerable amount of time and money is spent worldwide on the removal of barnacles from fouled vessels and other man-made structures exposed to the oceans. The adhesive proteins produced by many permanently attached marine organisms are remarkable in that they can function over wide temperature ranges, fluctuating salinity, humidity, and in the tides, waves and currents of marine environments. In contrast, the success of man-made adhesives in wet environments requires carefully cleaned surfaces which often must also be chemically treated and/or partially dried. Marine adhesives have also been explored for use as tissue glues in surgery and in dentistry, yet they are expensive to produce and can cause immune reactions. This project will develop simplified mimics of marine adhesives to identify the key components and processes require for the design and synthesis of superior adhesives for wet environments. The concepts developed in this proposal have potential to be further utilized to prepare degradable, synthetic polypeptide materials for downstream wet adhesion applications in areas such as medicine and dentistry. This funding will also be used to recruit and train women and underrepresented minority students in chemistry and materials research to contribute strongly to the STEM workforce.Technical AbstractThe performance and complexity of the proteins that are key polymeric components in marine mussel adhesives have received considerable attention in the past few decades. In addition to substantial efforts to study and decipher the biological processes, there has also been much effort to replicate mussel adhesive proteins (MAPs) using synthetic polymers. Synthetic polymers for wet adhesive applications offer potential advantages over biologically sourced proteins in terms of scalable production at low cost, absence of biological contaminants, and in some cases, improved properties for applications in medicine or industry. Many of these polymers have focused primarily on mimicking the 3,4-dehydroxyphenyl-L-alanine content of mussel proteins, but have paid less attention to many other functional groups and features of MAPs, such as hydrophobic and charged groups, as well as physical and chemical changes resulting from shifts in solution pH and redox potential. Although some efforts have attempted to mimic most if not all of these features in synthetic polymers, this remains a challenging problem, especially with respect to retaining amino acid sequence information and compositional uniformity. In this project, a new approach is proposed to address this challenge by mimicking MAP sequence information using uniform side-chain peptide sequences attached to homopolypeptide scaffolds designed to contain additional biomimetic functionality. The proposed studies aim to increase the level of functional sophistication in synthetic polymers closer toward true mimicry of the complexity found in multifunctional proteins. Knowledge gained from these studies will also yield scalable synthetic methods and design rules that can be applied to mimicry of other sequence specific protein materials. Outreach objectives in this proposal will continue current efforts developed by the PI in previous NSF-funded broader impacts in preparing women and underrepresented minority students for the STEM workforce.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.