HYBRID HYDROGELS SELF-ASSEMBLED FROM GRAFT COPOLYMERS

由接枝共聚物自组装的杂化水凝胶

• 批准号: 7173402
• 负责人: JINDRICH H. KOPECEK
• 金额: $ 28.71万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7173402
• 关键词: Abbreviations; Accounting; Acetic Acid; Acetic Acids; Affinity; Alanine; Arginine; Asparagine; Aspartic Acid; Atomic Force Microscopy; Biocompatible Materials; Biological; Biosensor; Characteristics; Charge; Circular Dichroism; Class; Coiled-Coil Domain; Compatible; Condition; Cyclohexanecarboxylic Acids; Cysteine; Dextrans; Differential Scanning Calorimetry; Drosophila genus; Drug Delivery Systems; Encapsulated; Environment; Equilibrium; Ethylene Glycols; Feedback; Flavin Mononucleotide; Fluorescence Resonance Energy Transfer; Glutamic Acid; Glutamine; Glycine; Goals; Guanidinium Chloride; Hand; Helix (Snails); Histidine; Hybrids; Hydrogels; Hydrophobic Interactions; Immunoglobulins; In Situ; Ionic Strengths; Ions; Isoleucine; Kinesin; Label; Length; Leucine; Liquid substance; Lysine; MALDI-TOF Mass Spectrometry; Mediating; Modeling; Molecular Sieve Chromatography; Molecular Structure; Molecular Weight; Muscle; N-(2-hydroxypropyl)methacrylamide; N-(4-carboxycyclohexylmethyl)maleimide N-hydroxysuccinimide ester; Nature; Numbers; Ornithine; Peptides; Permeability; Pharmaceutical Preparations; Phase Transition; Phenylalanine; Polyacrylamide Gel Electrophoresis; Polymerase Chain Reaction; Polymers; Process; Propane; Property; Proteins; Range; Rate; Recording of previous events; Research; Research Personnel; Sampling; Scanning Electron Microscopy; Serine; Side; Sodium Dodecyl Sulfate; Solutions; Solvents; Structure; Surface; Swelling; System; Temperature; Tertiary Protein Structure; Theoretical model; Tryptophan; Tyrosine; Valine; Vertebral column; aqueous; azobis(isobutyronitrile); base; copolymer; crosslink; cyclohexanecarboxylic acid; density; design; dextran; dimer; ear helix; epidoxorubicin glucuronide; ethylene glycol; hydroxypropyl methacrylate; macromolecule; methacrylamide; nanometer; programs; research study; self assembly; stimulus sensitivity; theories; tool

DESCRIPTION (provided by applicant): The goal of the project is to design new macromolecular structures, whose assembly into hybrid hydrogels will be modulated by association of coiled-coil peptide domains. N-(2-hydroxypropyl)rnethacrylamide (HPMA) copolymers containing coiled-coil domains as side-chains (grafts) will be synthesized by copolymerization of HPMA with macromonomers containing coiled-coils. The design of coiled-coil grafts imposes an antiparallel heterodimer formation in the self-assembly process. We hypothesize that the antiparallel orientation of heterodimers will contribute to the homogeneity of the self-assembled hybrid hydrogels due to the unique interchain dimer formation and decreased steric hindrance of the polymer backbone on the "in-register" alignment of heterodimers. Materials with tailor-made structures at the nanometer range will result from the proposed research. A theoretical model will be developed to assist in a rational design of the hybrid hydrogels. Experimental results will be analyzed using the model to provide feedback for the optimization of graft copolymer structure and of the self-assembly into hybrid hydrogels. The self-assembly of HPMA graft copolymers in the presence of encapsulated molecules will be evaluated in an attempt to develop new in-situ forming hybrid hydrogels for the delivery of proteins. The delivery system is suitable for a wide variety of biological molecules since the self-assembly occurs in aqueous media. The new hydrogels may find wide-ranging biomedical applications in drug delivery, biosensors, affinity separations, and nanoreactors. In addition, the possibility to join non-compatible materials, such as hydrophobic muscle mimics from liquid crystalline polymers and hydrogels, may open a new field of research.

描述（由申请人提供）： 该项目的目标是设计新的大分子结构，其组装成混合水凝胶将通过卷曲螺旋肽结构域的关联进行调节。通过 HPMA 与含有卷曲螺旋的大分子单体共聚，合成含有卷曲螺旋结构域作为侧链（接枝）的 N-(2-羟丙基)甲基丙烯酰胺 (HPMA) 共聚物。卷曲螺旋移植物的设计在自组装过程中强加了反平行异二聚体的形成。我们假设，由于独特的链间二聚体形成和异二聚体“对准”排列上聚合物主链的空间位阻减少，异二聚体的反平行取向将有助于自组装杂化水凝胶的均质性。拟议的研究将产生纳米范围内具有定制结构的材料。 将开发一个理论模型来帮助合理设计混合水凝胶。将使用该模型分析实验结果，为接枝共聚物结构的优化和自组装成杂化水凝胶提供反馈。 将评估 HPMA 接枝共聚物在封装分子存在下的自组装，以尝试开发用于蛋白质递送的新的原位形成杂化水凝胶。该输送系统适用于多种生物分子，因为自组装发生在水介质中。新型水凝胶可能在药物输送、生物传感器、亲和分离和纳米反应器等领域具有广泛的生物医学应用。此外，加入不相容材料的可能性，例如来自液晶聚合物和水凝胶的疏水性肌肉模拟物，可能会开辟一个新的研究领域。