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: 6967548
• 负责人: CHRISTINE E SCHMIDT
• 金额: $ 26.33万
• 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/6967548
• 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）：这些研究的目标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筛选技术已被用于选择一种独特的肽序列（“T59”），该序列特异性地与氯掺杂聚吡咯（PPyCl）紧密结合，PPyCl是一种导电聚合物，在生物医学应用中显示出前景，如神经再生。