Antifouling Peptide Mimetic Polymers

描述（由申请人提供）：治疗和诊断医疗器械暴露于生物液体通常伴随着蛋白质、细胞和微生物的界面吸附。表面的生物污染可能导致器械性能受损、成本增加，并且在某些情况下可能危及患者的生命。因此，消除或最大限度地减少非特异性生物分子-材料相互作用是改善当前和未来生物材料生物性能的一个组成部分。虽然几种聚合物涂层在防止蛋白质和细胞吸附在表面上方面取得了短期成功，但没有一种被证明是长期抗生物污损的理想选择。本研究的主要目标是设计和合成新型的持久的可降解聚合物，其化学和结构特性最适合于防止生物界面处的蛋白质污染。这些聚合物由两个不同的结构域耦合在一起-锚定结构域的灵感来自贻贝分泌的粘附蛋白附着在海洋表面，和一个多聚（N-取代甘氨酸）的“类肽”段设计抵抗蛋白质和细胞的附着。将合成具有各种组成、长度和结构的拟肽聚合物，并将进行高灵敏度蛋白质吸附实验以测试这些聚合物的蛋白质抗性。蛋白质吸附实验将指导，并确认，使用分子理论，特别适合于研究蛋白质与接枝聚合物的相互作用的系统的理论计算。这种系统的耦合实验/理论研究是很难完成与传统的合成聚合物，但有利于在我们的情况下，通过精确控制拟肽聚合物的结构，分子量和组成。这项研究的结果将包括对生物聚合物基本特性的新见解，以及识别能够限制治疗和诊断设备表面的蛋白质和细胞污染的新生物启发聚合物。在这项研究中，我们将结合联合收割机的理论和实验方法来研究一类新的仿生聚合物的生物相容性。当应用于物体的表面时，这些聚合物预期通过提供对蛋白质、细胞和细菌污染的抵抗性来增强医疗装置的性能。

DESCRIPTION (provided by applicant): Exposure of therapeutic and diagnostic medical devices to biological fluids is often accompanied by interfacial adsorption of proteins, cells and microorganisms. Biofouling of surfaces can lead to compromised device performance, increased cost, and in some cases may be life-threatening to the patient. The elimination or minimization of nonspecific biomolecule-material interactions is therefore an integral part of refining the biological performance of current and future biomaterials. Although several antifouling polymer coatings have enjoyed short-term success in preventing protein and cell adsorption on surfaces, none have proven ideal for conferring long-term biofouling resistance. The primary goal of this study is to design and synthesize novel long-lasting antifouling polymers with chemical and structural characteristics optimal for preventing protein fouling at biointerfaces. These polymers consist of two distinct domains coupled together- an anchoring domain inspired by the adhesive proteins secreted by mussels for attachment to marine surfaces, and an antifouling poly(N-substituted glycine) "peptoid" segment designed to resist protein and cellular attachment. Peptidomimetic polymers with a variety of compositions, lengths, and architectures will be synthesized, and high sensitivity protein adsorption experiments will be performed to test the protein resistance of these polymers. The protein adsorption experiments will be both guided by, and confirmed with, theoretical calculations of the systems using a molecular theory that is particularly well-suited to investigating protein interactions with grafted polymers. Such systematic coupled experimental/theoretical investigations are difficult to accomplish with traditional synthetic polymers, but are facilitated in our case by the precise control of peptidomimetic polymer architecture, molecular weight, and composition. Outcomes of this study will include new insights into fundamental properties of antifouling polymers, as well as identification of new biologically inspired polymers capable of limiting protein and cell fouling of therapeutic and diagnostic device surfaces. PUBLIC HEALTH REVELANCE In this study we will combine theoretical and experimental approaches to study the antifouling properties of a new class of biomimetic polymers. When applied to the surface of an object, these polymers are anticipated to enhance the performance of medical devices by providing resistance to fouling by proteins, cells and bacteria.