Mussel-inspirit polymerization: „The enzyme free route of an tyrosinase activated polymerization“

该提案的研究目的是引入一类新的大单体，它提供了在酶激活后表现聚合的可能性。通过酶活化聚合，可以得到具有多官能团性质的节段共聚物。聚合过程源于贻贝粘附过程中发生的基本交联原理。在贻贝足足形成过程中导致贻贝足蛋白之间交联的类似化学反应应该用于产生具有重复单体序列的线性聚合物。在贻贝粘附过程中，酶控制的过程发生，同步激活和交联一组贻贝足蛋白。该过程是高度复杂的，远未被完全理解，但基本的交联原理可以抽象和应用于线性聚合设计的寡肽（大单体），产生分段共聚物。酶活化和可聚合的寡肽需要有一个酪氨酸残基和一个赖氨酸或半胱氨酸残基。这将允许两步聚合过程发生：首先，不可聚合的寡肽将被酪氨酸酶激活，从酪氨酸残基产生3,4-二羟基苯丙氨酸衍生物（L-Dopa衍生物）。随后，聚合可以通过多加成机制发生，包括赖氨酸或半胱氨酸（氨基或硫醇）的亲核侧链官能团与L-Dopa衍生物相互加成，分别产生赖氨酸基- dopa或环氨酸基- dopa偶联产物。在该项目中，将研究酪氨酸酶可活化大单体的最低要求以及该过程对偏离生物衍生酪氨酸酶底物的最大耐受性。合成了一组功能单体，研究了酪氨酸酶的活化动力学及其聚合机理。聚合过程将适应1-10克的大单体的更大规模，多功能聚合物将被深入表征，然后作为各种材料表面的涂层进行测试。除了揭示生物粘附的基本方面外，还将访问可能具有粘合剂，（纳米）颗粒稳定剂或晶体生长调节剂潜力的有趣聚合物。

Research objective of the proposal is the introduction of a novel class of macromonomers, which provides the possibility to exhibit a polymerization after being enzymatically activated. As a result of the enzyme activated polymerization, segmented copolymers with multifunctional character will be obtained. The polymerization process is derived from the fundamental cross-linking principle occurring in mussel adhesion processes. Similar chemistry that leads during byssus formation of marine mussels to cross-links between mussel foot proteins should be employed to generate linear polymers with repetitive monomer sequences.During mussel adhesion, enzymatically controlled processes occur, which synchronize the activation and crosslinking of a set of mussel foot proteins. The process is highly complex and far from being fully understood, but the fundamental cross-linking principle can be abstracted and applied towards linear polymerization of designed oligopeptides (macromonomers) yielding segmented copolymers.The enzymatically activatable and polymerizable oligopeptides require to have one tyrosine residue and one lysine or cysteine residue. This will allow for the two-step polymerization process to occur: First the non-polymerizalble oligopeptide will be enzymatically activated by tyrosinase, generating a 3,4-dihydroxyphenylalanin derivative (L-Dopa derivative) from the tyrosine residue. Subsequently, polymerization can occur by polyaddition mechanism involving the michel addition of the nucleophilic side chain functionality of lysine or cysteine (amino or thiol) to the L-Dopa derivative leading to lysinyl-DOPA- or cycteinyl-DOPA coupling products, respectively.Within the project the minimum requirements for a tyrosinase activatable macromonomer and the maximum tolerance of the process towards deviation from biologically derived tyrosinase substrates will be investigated. A set of functional macromonomers will be synthesized, the tyrosinase activation-kinetics and the following polymerization mechanism will be investigated. The polymerization process will be adapted to a larger scale of up to 1-10 g macromonomers and the multifunctional polymers will be deeply characterized, before being tested as coatings for various material surfaces. Besides revealing insight into fundamental aspects of bioadhesion, interesting polymers will be accessed that might have potential as adhesives, (nano)particle stabilizers, or crystal growth modifiers.