Synthesis and properties of glycopolypeptide biohybrid materials Theme: Novel Polymer Synthesis and New Supramolecular Polymer Assemblies

近年来，合成多肽领域取得了许多重大进展，包括对形成囊泡、原纤维和其他在医学和材料化学中具有潜在应用的结构的嵌段和杂合共聚肽的研究。然而，糖基化多肽的开发没有跟上步伐，主要是由于不能以受控的方式容易地合成糖多肽。天然蛋白质的糖基化提供了多种功能，如识别事件的介导、蛋白质构象的修饰、蛋白酶的保护以及眼睛和关节的润滑。我们的目标是制备糖基化多肽和多糖多肽生物杂合物，并控制糖功能的放置。我们预计这些材料将表现出新颖的结构和物理性质，并在包含在核壳颗粒、囊泡和水凝胶中时调整生物相容性和细胞结合能力。我们的团队结合了来自四个国家的专业知识，包括多肽合成，聚合物类似反应，自组装材料的制备和表征，以及细胞培养和动物模型中自组装的评估。我们将开发不同但互补的策略来制备糖肽聚合物，这将使我们能够制备比我们任何团队单独生产的材料更多样化的材料。我们的方法包括：新的糖-氨基酸单体的受控聚合、糖与多肽的叠氮-炔和硫醇-烯缀合、以及寡糖和多肽的链端和侧链偶联。我们将共同努力，将这些方法联合收割机用于制备前所未有的含有多种类型糖功能的嵌段糖肽，用于自组装材料。将对这些材料进行表征，以确定糖键和糖官能团沿链的沿着位置如何影响物理、结构和生化性质。我们的方法的一个关键优势是，复杂的糖共聚物将以快速和可扩展的方式制备，这允许通过仔细调整组成和结构来微调性质。

The field of synthetic polypeptides has seen many significant advances in recent years, including studies on block and hybrid copolypeptides that form vesicles, fibrils, and other structures with potential applications in medicine and materials chemistry. However, the development of glycosylated polypeptides has not kept pace, primarily due to the inability to readily synthesize glycopolypeptides in a controlled manner. Glycosylation of natural proteins provides diverse functionality such as mediation of recognition events, modification of protein conformations, protection from proteases, and lubrication in eyes and joints. Our goal is to prepare glycosylated polypeptides and polysaccharidepolypeptide biohybrids with controlled placement of sugar functionality. We expect these materials will display novel structural and physical properties, and will tune biocompatibility and cell-binding ability when included in core-shell particles, vesicles and hydrogels. Our group combines expertise from four countries in polypeptide synthesis, polymer-analogous reactions, preparation and characterization of self-assembled materials, and evaluation of self-assemblies in cell culture and animal models. We will develop different yet complimentary strategies to prepare glycopeptide polymers, which will allow us to prepare a more diverse range of materials than any of our team could produce separately. Our methods include: controlled polymerization of new glyco-amino acid monomers, azide-alkyne and thiol-ene conjugation of sugars onto polypeptides, and chain-end and side-chain coupling of oligosaccharides and polypeptides. We will work together to combine these methods for preparation of unprecedented block glycopeptides containing multiple types of sugar functionality for use in self-assembling materials. These materials will be characterized to determine how the sugar linkage and placement of sugar functionality along the chain influences physical, structural and biochemical properties. A key advantage of our approach is that complex glycopolymers will be prepared in a rapid and scalable manner, which allows fine tuning of properties through careful adjustment of compositions and architectures.