Macromolecular nano-objects from peptide-hybrid block copolymers

本研究的重点是设计和制备具有特定尺寸和形状的大分子纳米物体，方法是通过多肽基二嵌段共聚物在水溶液中的自组装以及对所产生的超分子组装体进行共价后修饰。嵌段共聚物的肽段具有一些独特的特征，包括进行定向氢键相互作用的能力，采用明确的二级结构，并组装成明确的高阶蛋白质结构域结构。在某些情况下，环境参数变化引起的构象变化可用于逆转这些组装过程。本提案旨在探索肽块的这些特殊特征，以制备前所未有的超分子组装，这些超分子组装可以被共价捕获并转化为靶向杂交纳米物体。将探讨两类嵌段共聚物构建块；第一类由疏水聚（丁二烯）或聚（异戊二烯）嵌段和亲水肽段组成，第二类由亲水聚（乙二醇）嵌段和具有精确定义的氨基酸序列的完全单分散的肽段组成。第一类构建块的自组装主要是由嵌段共聚物的两亲性特性驱动的，而在第二类情况下，蛋白质折叠基序的形成为自组装提供了非常具体的驱动力。为了制备具有几何形状的纳米物体，必须开发交联策略，以便在不影响大小或形状的情况下对超分子组装进行共价捕获。由于其明确的几何形状和交联后获得的机械稳定性，纳米物体具有堆积成可预测的超晶格的倾向。利用各种逐层组装方法，将尝试探索纳米物体的这些特性，以制备具有有趣的光学或机电性能的超分子材料，并开发用于生物医学目的的超薄水凝胶层。将研究构象变化在多大程度上可以用于可逆地切换非线性光学和/或压电活性，调节吸收和释放特性并操纵这些材料的膨胀行为。

This proposal focuses on the design and preparation of macromolecular nano-objects of defined size and shape via self-assembly of peptide-based diblock copolymers in aqueous solution and covalent post-modification of the resulting supramolecular assemblies. The peptide segments of the block copolymers poses some unique features, including the ability to undergo directed hydrogen bonding interactions, to adopt defined secondary structures and to assemble into well-defined higher-order protein domain structures. In some cases, conformational changes by variations in environmental parameters can be used to reverse these assembly processes. This proposal seeks to explore these peculiar characteristics of the peptide blocks for the preparation of unprecedented supramolecular assemblies, which can be covalently captured and transformed into the targeted hybrid nano-objects. Two classes of block copolymer building blocks will be explored; one class composed of a hydrophobic poly(butadiene) or poly(isoprene) block and a hydrophilic peptide segment, and a second class comprised of a hydrophilic poly(ethylene glycol) block and a perfectly monodisperse peptide segment with a precisely defined amino acid sequence. The self-assembly of the first class of building blocks is primarily driven by the amphiphilic character of the block copolymers, whereas in the second case the formation of protein folding motifs provides a very specific driving force for self-assembly. For the preparation of nano-objects with geometries, crosslinking strategies will have to be developed that allow covalent capture of the supramolecular assemblies without affecting size or shape. Due to their well-defined geometry and the mechanical stability obtained after crosslinking, the nano-objects have the propensity to pack into predictable superlattices. Using various layer-by-layer assembly methods, it will be attempted to explore these characteristics of the nano-objects for the preparation of supramolecular materials with interesting optical or electro-mechanical properties and for the development of ultrathin hydrogel layers for biomedical purposes. It will be investigated to which extent conformational changes can be used to reversibly switch the non-linear optical and/or piezoelectric activity, to modulate the uptake and release characteristics and manipulate the swelling behaviour of these materials.