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

非技术摘要许多海洋生物的多产黏附能力是众所周知的。每年，全世界都要花费大量的时间和金钱从受污染的船只和暴露在海洋中的其他人造建筑物上拆除藤壶。许多永久附着的海洋生物产生的粘附性蛋白的显著之处在于，它们可以在广泛的温度范围、波动的盐度、湿度以及海洋环境的潮汐、海浪和洋流中发挥作用。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，这些表面通常还必须经过化学处理和/或部分干燥。海洋粘合剂也被探索用于外科和牙科的组织胶，但它们的生产成本很高，而且会引起免疫反应。该项目将开发简化的船用胶粘剂模拟，以确定设计和合成用于潮湿环境的优质胶粘剂所需的关键组件和工艺。本提案中开发的概念有可能进一步用于制备可降解的合成多肽材料，用于医药和牙科等领域的下游湿式粘合应用。这笔资金还将用于招募和培训化学和材料研究方面的女性和代表性较低的少数族裔学生，以便为STEM工作做出重大贡献。技术摘要在过去几十年里，作为海洋贻贝粘合剂中关键聚合成分的蛋白质的性能和复杂性受到了相当大的关注。除了大量的努力来研究和破译生物过程，也有很多努力来复制贻贝黏附蛋白(MAP)使用合成聚合物。与生物来源的蛋白质相比，用于湿式粘合剂应用的合成聚合物在以下方面具有潜在的优势：低成本可扩展生产、无生物污染，在某些情况下还可改善医药或工业应用的性能。许多聚合物主要关注于模拟贻贝蛋白质的3，4-脱羟基苯基-L-丙氨酸含量，而较少关注许多其他官能团和图谱的特征，如疏水基团和带电基团，以及由于溶液pH和氧化还原电位变化而引起的物理和化学变化。尽管一些努力试图在合成聚合物中模拟这些特征中的大部分，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一致性方面。在这个项目中，提出了一种新的方法来应对这一挑战，方法是使用附着在同源多肽支架上的统一侧链多肽序列来模拟MAP序列信息，以包含额外的仿生功能。拟议的研究旨在提高合成聚合物的功能复杂性水平，更接近于真正模拟多功能蛋白质中的复杂性。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，这些方法和设计规则可以应用于模仿其他序列特定的蛋白质材料。这项提案中的外展目标将继续由PI在之前的NSF资助的更广泛的影响中制定的当前努力，为STEM劳动力培养女性和代表不足的少数族裔学生。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.