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

在本提案中，研究了超快速环境温度和无催化剂偶联化学，以将单体序列定义的肽结合到生物聚合物表面上。目标将是最终开发一种肽修饰生物底物的途径，其中肽段构成诸如特定细胞粘附，生物杀灭活性或结晶过程调节等功能。目前的建议将证明，极其温和和无催化剂的偶联策略非常适合将敏感的生物分子连接到生物底物上。项目的总体目标被细分为单独的工作包，每个工作包都有自己明确的目标。这些是(i)可变聚（糖）表面的预功能化和表征，例如纤维素，几丁质，壳聚糖和透明质酸体系，具有高度缺电子的二硫酯；（ii）建立一种合成方法，将二硫酯或环戊二烯基部分引入到负载肽中，包括这些在均相溶液中与合成聚合物或可溶性聚（糖）偶联的模型研究；（iii）用肽序列修饰缺乏电子的二硫酯修饰的聚（糖）表面的功能化以及对生成的表面的深入表征，以及（iv）应用开发的超快速室温接枝工艺制备功能底物。

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.