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生物分子复合材料。作为初步研究的一部分，联合肽噬菌体展示库和生物瞬间技术已被用于选择独特的肽序列（“ T59”），该肽序列（“ T59”）专门并直接与氯掺于氯的型多吡咯（PPYCL）（PPYCL）（PPYCL）（PPYCL），一种具有电导性聚合物，该聚合物在生物疗法中表现出了有望的，例如生物疗法，例如新的Neversever Regeniver inserve receneration，例如Noversever inserve inserve recenition。 在拟议的研究中，将研究T59肽相互作用与PPYCL（体外和体内）的结合亲和力和稳定性以及这种相互作用的性质。该信息将有助于理解表面相互作用和生物材料修饰策略，并且对于有效地应用这些序列的体外（例如生物传感器）或体内（例如组织工程）应用至关重要。 PPYCL还将用大型生物分子（例如NGF）进行功能化，以说明这种方法的多功能性和效用。这些目标将在以下特定目的中实现：（1）研究对T59修改的体内对PPYCL的反应； （2）使用荧光胺蛋白测定，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）将化学和聚合物类似物与肽变体（使用结合能量的建模和模拟设计）一起研究T59和PPYCL之间的相互作用机制； （4）研究通过T59肽将大生物分子（即神经生长因子或NGF）连接到PPYCL的能力。 总体而言，这些研究将探讨一种用于修饰组织工程应用合成聚合物的替代方法。通过选择和识别与合成聚合物高亲和力相互作用的独特肽序列，可以轻松地使用这些肽来修饰聚合物表面（即，可以在一个端上与聚合物结合序列合成肽，并在一个末端与聚合物结合序列合成，并与细胞，药物，生长因子等结合的序列等）。这种表面修饰的策略可以用作使用现有聚合物开发生物活性材料的多功能方法（包括已经批准的FDA的聚合物和/或缺乏功能性化学基团用于耦合反应的聚合物，例如PPYCL，而无需更改材料的大量性质。