Synthetic oligomers as functional modules to mimic complex adsorption mechanisms of peptide-based adhesion domains

精密聚合物化学领域提供了快速增长的合成工具，使精密聚合物链段常规可用。然而，实现功能序列，充分利用这些信息丰富的大分子的能力仍然是在开始。本研究计划的目的是合成和研究精确的聚合物片段，以模仿基于肽的粘附结构域用于Al 2 O3结合的优异涂层性能。最近已通过噬菌体展示选择12聚体序列作为酪氨酸酶可活化的粘合剂用于Al 2 O3表面。该肽证明了显着的结合动力学和生成的涂层对海水模型条件下具有高稳定性。现代NMR光谱结合计算分子建模提供了分子水平上的见解，揭示了强结合子域与动态结合子域相结合的存在，作为实现优异涂层动力学的关键。将采用依赖于将肽序列直接翻译成精确聚合物片段的功能序列的既定设计策略。通过侧链官能团的一对一映射，针对强结合亚结构域和动态结合亚结构域鉴定的关键序列将被翻译成功能性精确聚合物序列。应用硫代内酯/迈克尔化学的固相支持合成将提供序列限定的低聚（酰胺氨基甲酸酯），并且在单单元单体插入（SUMI）条件下的受控自由基聚合将产生单分散的低聚（丙烯酸酯）。将合成包括直接翻译的母序列和系统序列变异的片段组，并研究成膜动力学和涂层稳定性。两个片段（强+动态）的组合提供了精密聚合物，将研究其有效的涂层特性，因为这些可能模拟在母体肽中发现的复杂吸附机制的方面。通过比较不同精密平台的涂层性能，可以更好地了解侧链官能度序列和骨架化学对涂层动力学和稳定性的相关性。有效的涂层材料对于改善防腐蚀、防污染或粘合剂应用至关重要。然而，随着寡肽序列-结构-功能关系的分子理解的进展，可以预期通过合成的非肽精密聚合物重建广泛的序列特异性功能。其中，材料选择性胶水或相容剂的纳米界面管理的复合材料可能会得到可能。为了实现这些高级功能，这将是难以获得的既定聚合物，可能合法的合成努力，精确的聚合物合成。

The field of precision polymer chemistry provides a rapidly growing number of synthesis tools that make precision polymer segments routinely available. However, realizing functional sequences to fully exploit the capabilities of these information rich macromolecules is still at the onset. Objective of the research proposal is to synthesize and investigate precision polymer segments that mimic the excellent coating properties of a peptide-based adhesion domain for Al2O3 binding. The 12mer sequence has been recently selected by phage-display as a tyrosinase activable binder for Al2O3 surfaces. The peptide proved remarkable binding kinetics and generated coatings with high stabilities against seawater model conditions. Modern NMR spectroscopy in conjunction with computational molecular modelling provided insights on the molecular level, revealing the presence of a strong binding subdomain combined with a dynamically binding subdomain as a key to realize the excellent coating kinetics. The established design strategy, relying on the direct translation of a peptide sequence into functional sequences of precision polymer segments will be employed. By one-to-one mapping of side chain functionalities the key sequences identified for the strong binding subdomain and those for the dynamic binding subdomain will be translated into functional precision polymer sequences. Solid-phase supported synthesis applying thiolactone/Michael-chemistry will provide sequence defined oligo(amid urethane)s and controlled radical polymerization under single unit monomer insertion (SUMI) conditions will yield monodisperse oligo(acrylate)s. Sets of segments including the directly translated mother sequences and systematic sequence variations will be synthesized and investigated on film formation kinetics and coating stability. The combination of both segments (strong+dynamic) provides precision polymers that will be investigated for effective coating properties as these might mimic aspects of the complex adsorption mechanism found in the parent peptide. The comparison between the coating properties of different precision platforms allows to improve the understanding of the relevance of the sidechain functionality sequences and backbone chemistry on both, the coating kinetics and stability.Effective coating materials are essential to improve anti-corrosion, anti-fouling or adhesive applications. However, with advances in molecular understanding of oligopeptide sequence-structure-function relationships one can anticipate a broad range of sequence specific functions to be rebuilt via synthetic, non-peptidic precision polymers. Among those, material selective glues or compatibilizers for nano-interface management in composites might get possible. To realize such advanced functions, that would be difficult to be accessed by established polymers, might legitimate the synthetic efforts of precision polymer synthesis.