Orthogonal Modification of Biopolymers with Variable Peptide Sequences via Ultra-Rapid Covalent Modification

在本方案中，研究了利用超快的常温和无催化剂的偶联化学将单体序列定义的多肽结合到生物聚合物表面。其目标是最终开发一条获得多肽修饰生物底物的途径，其中多肽片段构成特定的细胞黏附、杀生活性或调节结晶过程的功能。目前的提案将证明，极其温和和无催化剂的偶联策略非常适合于将敏感的生物分子连接到生物底物上。该项目的总体目标被细分为单独的工作包，这些工作包有各自明确的目标。这些是(I)具有高度缺乏电子的二硫代酯的可变多(糖)表面的预官能化和表征，例如纤维素、甲壳素、壳聚糖和透明质酸体系，(Ii)将二硫代酯或环戊二烯基引入支撑肽的合成方法的建立，包括这些在均相溶液中与合成聚合物或可溶性多(糖)偶联的模型研究，(Iii)具有肽序列的缺电子二硫代酯修饰的多(糖)表面的官能化以及生成表面的深入表征，以及(Iv)应用所开发的超快速常温接枝方法制备功能底物。

In the present proposal, ultra-rapid ambient temperature and catalyst-free coupling chemistry is investigated to be employed to bind monomer sequence-defined peptides onto biopolymer based surfaces. The aim will be to ultimately develop an access route to peptide modified biosubstrates, where the peptide segments constitute functions such as specific cell adhesion, biocidal activity or modulation of crystallization processes. The current proposal will demonstrate that extremely mild and catalyst-free conjugation strategies are ideally suited to ligate sensitive biomolecules to biological substrates.The overall aim of the project is subdivided into individual work packages, which have well-defined aims of their own. These are (i) the pre-functionalization and characterization of variable poly(saccharide) surfaces, e.g. cellulose, chitin, chitosan and hyaluronic acid systems, with highly electron deficient dithioesters, (ii) the establishment of a synthetic methodology to introduce dithioester or cyclopentadienyl moieties to supported peptides including model studies of the coupling of these in homogenous solution to synthetic polymers or soluble poly(saccharides), (iii) the functionalization of the electron deficient dithioester decorated poly(saccharide) surfaces with peptide sequences as well as the in-depth characterization of the generated surfaces, and (iv) the application of the developed ultra-rapid ambient temperature grafting procedure for the preparation of functional substrates.