Antifouling Peptide Mimetic Polymers

描述(申请人提供)：治疗和诊断医疗设备暴露在生物流体中通常伴随着蛋白质、细胞和微生物的界面吸附。表面的生物污垢会导致设备性能下降，成本增加，在某些情况下可能会危及患者的生命。因此，消除或最小化非特定生物分子与材料的相互作用是提炼当前和未来生物材料生物学性能的重要组成部分。尽管几种防污聚合物涂层在防止蛋白质和细胞在表面吸附方面取得了短期成功，但没有一种涂层被证明是赋予长期生物防污性能的理想选择。这项研究的主要目标是设计和合成具有最佳化学和结构特征的新型长效防污聚合物，以防止生物界面上的蛋白质结垢。这些聚合物由两个连接在一起的不同结构域组成-一个锚定结构域受到贻贝分泌的粘附性蛋白质的启发，用于附着在海洋表面，以及一个防污聚(N-取代甘氨酸)“类肽”片段，旨在抵抗蛋白质和细胞的附着。将合成具有不同组成、长度和结构的模拟多肽聚合物，并将进行高灵敏度的蛋白质吸附实验来测试这些聚合物的蛋白质抗性。蛋白质吸附实验将由使用特别适合研究蛋白质与接枝聚合物相互作用的分子理论的体系的理论计算指导并得到证实。这种系统的实验/理论耦合研究很难用传统的合成聚合物完成，但在我们的情况下，通过精确控制多肽聚合物的结构、相对分子质量和组成，可以促进这种系统的耦合实验/理论研究。这项研究的结果将包括对防污聚合物的基本性质的新见解，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垢的新的生物启发聚合物。在这项研究中，我们将结合理论和实验方法来研究一类新型仿生聚合物的防污性能。当应用于物体表面时，这些聚合物有望通过提供对蛋白质、细胞和细菌污染的抵抗力来增强医疗设备的性能。

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.