Antifouling Peptide Mimetic Polymers

防污肽模拟聚合物

• 批准号: 7802741
• 负责人: Phillip B Messersmith
• 金额: $ 7.91万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-10 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7802741
• 关键词: Adhesions; Adhesives; Adsorption; Albumins; Architecture; Bacteria; Behavior; Biocompatible Materials; Biological; Biomimetics; Biosensor; Blood; Cardiovascular system; Cell Communication; Cell physiology; Cell-Matrix Junction; Cells; Characteristics; Chemicals; Chemistry; Classification; Complex; Contact Lenses; Coupled; DNA; Development; Devices; Diagnostic; Dialysis procedure; Enzymes; Equilibrium; Exhibits; Fibrinogen; Future; Goals; Healthcare; In Vitro; Individual; Indwelling Catheter; Investigation; Kinetics; Knowledge; Lead; Length; Life; Liquid substance; Marines; Medical Device; Medical Technology; Methods; Microfluidic Microchips; Molecular; Molecular Weight; Muramidase; Mussels; N-substituted Glycines; Outcome Study; Patients; Peptide Hydrolases; Peptides; Peptoids; Performance; Phase; Polymers; Preparation; Property; Protein Microchips; Proteins; Public Health; Research; Resistance; Role; Secure; Serum; Solid; Stents; Surface; System; Technology; Testing; Therapeutic; Time; Tissues; Vertebral column; adhesive protein (mussel); cost; density; design; improved; in vivo; innovation; insight; interfacial; macromolecule; meetings; microorganism; mimetics; monolayer; nanoparticle; novel; peptidomimetics; prevent; research study; success; surface coating; synthetic peptide; theories; ventricular assist device

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.

描述（由申请人提供）：将治疗和诊断医疗设备暴露于生物流体中，通常伴随着蛋白质，细胞和微生物的界面吸附。表面的生物污染会导致设备的性能损害，成本提高，在某些情况下可能会对患者威胁生命。因此，消除或最小化非特异性生物分子材料相互作用是完善当前和未来生物材料的生物学性能的组成部分。尽管几种防染色聚合物涂层在防止表面上的蛋白质和细胞吸附方面取得了短暂的成功，但事实证明，没有人能够赋予长期生物污染性的耐药性。这项研究的主要目的是设计和合成具有化学和结构特征的新型持久防染色聚合物，以防止生物界面处的蛋白质结垢。这些聚合物由两个不同的结构域组成 - 由贻贝分泌的粘合剂蛋白启发为锚定结构域，以及用于固定在海洋表面上的粘附蛋白，以及一个针对抗蛋白质和细胞附着的抗裂解聚（N-取代的甘氨酸）“肽”段。将合成具有多种组合物，长度和体系结构的肽型聚合物，并将进行高灵敏度蛋白吸附实验，以测试这些聚合物的蛋白质耐药性。蛋白质吸附实验将由分子理论对系统的理论计​​算进行指导并确认，该理论特别适合研究与移植聚合物的蛋白质相互作用。这种系统的实验/理论研究很难用传统的合成聚合物来完成，但在我们的情况下，通过精确控制肽的聚合物结构，分子量和组成，可以促进。这项研究的结果将包括对抗污染聚合物的基本特性的新见解，以及鉴定能够限制蛋白质和细胞结垢的新型生物学启发的聚合物。在这项研究中，我们将结合理论和实验方法来研究新的仿生聚合物的防污特性。当应用于物体的表面时，预计这些聚合物可以通过提供蛋白质，细胞和细菌对结垢的阻力来增强医疗设备的性能。