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数量迅速增长的合成工具，使精密聚合物链段成为常规可用。然而，实现功能序列以充分利用这些信息丰富的大分子的能力仍处于起步阶段。该研究计划的目的是合成和研究精确的聚合物链段，以模拟用于结合氧化铝的基于多肽的粘附域的优异涂层性能。最近，噬菌体展示技术选择了12聚体序列作为氧化铝表面酪氨酸酶活性结合剂。该多肽具有显著的结合动力学，并在海水模拟条件下生成了稳定性较高的涂层。现代核磁共振波谱与计算分子模拟相结合，在分子水平上提供了洞察力，揭示了强结合亚域和动态结合亚域的存在是实现优异涂层动力学的关键。将采用已建立的设计策略，依赖于将肽序列直接翻译成精密聚合物链段的功能序列。通过侧链功能的一对一映射，确定的强结合亚区的关键序列和动态结合亚域的关键序列将被翻译成功能精密的聚合物序列。应用硫内酯/迈克尔化学的固相支撑合成将得到序列确定的低聚(在氨酯中)S，而在单体插入(SUMI)条件下的受控自由基聚合将得到单分散的低聚(丙烯酸酯)S。这两个链段的组合(强+动态)提供了精密聚合物，将研究其有效的涂层性能，因为这些可能模仿在母肽中发现的复杂吸附机制的各个方面。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团序列和骨架化学对两者的相关性、涂层动力学和稳定性。有效的涂层材料对于提高防腐、防污或粘接应用至关重要。然而，随着对寡肽序列-结构-功能关系的分子理解的进步，人们可以预期通过合成的非肽精密聚合物来重建广泛的序列特定功能。其中，用于复合材料纳米界面管理的材料选择性胶或相容剂可能成为可能。要实现现有聚合物难以实现的这些高级功能，可能会使精密聚合物合成的合成努力合法化。

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.