Fabrication of Novel Biomimetic Polymers Using Combinatorial Peptide Screening

利用组合肽筛选制备新型仿生聚合物

• 批准号: 7093464
• 负责人: CHRISTINE E SCHMIDT
• 金额: $ 25.68万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-07 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7093464
• 关键词: atomic force microscopy; biomaterial development /preparation; biomimetics; calorimetry; chemical binding; chemical conjugate; combinatorial chemistry; laboratory rat; nerve growth factors; peptide library; phage display; polymers; pyrroles; thermodynamics

DESCRIPTION (provided by applicant): The goal of these studies is to develop and characterize unique synthetic polymer-biological molecule composites for biomedical applications. As part of preliminary studies, combinatorial peptide phage display libraries and biopanning techniques have been used to select a unique peptide sequence ("T59") that specifically and tightly binds directly to chlorine-doped polypyrrole (PPyCl), an electrically conductive polymer that has shown promise in biomedical applications, such as nerve regeneration. In the proposed studies, the binding affinity and stability of the T59 peptide interaction with PPyCl (both in vitro and in vivo) and the nature of this interaction will be investigated. This information will contribute to the understanding of surface interactions and biomaterials modification strategies, and is critical for effectively applying these sequences for either in vitro (e.g., biosensor) or in vivo (e.g., tissue engineering) applications. PPyCl will also be functionalized with large biomolecules (e.g., NGF) to illustrate the versatility and utility of this approach. These goals will be accomplished in the following Specific Aims: (1) Study the in vivo response to PPyCl modified with T59; (2) quantitatively analyze, using fluorescamine protein assays, atomic force microscopy, and isothermal titration calorimetry, the binding of T59 to PPyCl; (3) use chemical and polymer analogs in conjunction with peptide variants (designed using modeling and simulations of binding energetics) to study the mechanism of interaction between T59 and PPyCl; and (4) study the ability to attach large biomolecules (i.e., nerve growth factor or NGF) to PPyCl via the T59 peptide. Overall, these studies will explore an alternate approach for modifying synthetic polymers for tissue engineering applications. By selecting and identifying unique peptide sequences that interact with high affinity to synthetic polymers, one can easily modify the polymer surfaces using those peptides (i.e., peptides can be synthesized with the polymer binding sequence on one end, and a sequence that binds to cells, drugs, growth factors, etc. on the other end). This strategy for surface modification could serve as a versatile method to develop bioactive materials using existing polymers (including those that are already FDA approved and/or those polymers that lack functional chemical groups for coupling reactions, like PPyCl), without changing the bulk properties of the materials.

描述（由申请人提供）：这些研究的目的是开发和表征用于生物医学应用的独特合成聚合物-生物分子复合材料。作为初步研究的一部分，组合肽噬菌体展示文库和生物淘选技术已被用于选择特异性地和紧密地直接结合到氯掺杂的聚吡咯（PPyCl）的独特肽序列（“T59”），所述聚吡咯是一种导电聚合物，其在生物医学应用（例如神经再生）中显示出前景。 在拟定的研究中，将研究T59肽与PPyCl相互作用的结合亲和力和稳定性（体外和体内）以及这种相互作用的性质。这些信息将有助于理解表面相互作用和生物材料改性策略，并且对于有效地将这些序列应用于体外（例如，生物传感器）或体内（例如，组织工程）应用。PPyCl还将用大生物分子（例如，NGF）来说明这种方法的多功能性和实用性。这些目标将在以下具体目标中实现：（1）研究T59修饰的PPyCl的体内反应：（2）用荧光蛋白测定、原子力显微镜和等温滴定量热法定量分析T59与PPyCl的结合;（3）结合肽变体使用化学和聚合物类似物（使用结合能量学的建模和模拟设计）来研究T59和PPyCl之间的相互作用机制;和（4）研究附着大生物分子的能力（即，神经生长因子或NGF）通过T59肽转化为PPyCl。 总的来说，这些研究将探索一种替代的方法来修改合成聚合物的组织工程应用。通过选择和鉴定以高亲和力与合成聚合物相互作用的独特肽序列，可以容易地使用那些肽修饰聚合物表面（即，可以合成一端具有聚合物结合序列，另一端具有与细胞、药物、生长因子等结合的序列的肽）。这种表面改性的策略可以作为一种通用的方法，使用现有的聚合物（包括那些已经被FDA批准的聚合物和/或那些缺乏用于偶联反应的功能化学基团的聚合物，如PPyCl）开发生物活性材料，而不改变材料的整体性能。