Biomimetic Receptors for Small Hydrophobic Drugs, Carbohydrates, and Oligopeptides

小疏水药物、碳水化合物和寡肽的仿生受体

• 批准号: 8853438
• 负责人: Yan Zhao
• 金额: $ 26.38万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8853438
• 关键词: Adoption; Affinity; Affinity Chromatography; Alkaloids; Antibodies; Binding; Binding Sites; Biological; Biological Process; Biology; Biomedical Engineering; Biomimetics; Biotechnology; Boronic Acids; Caliber; Carbohydrates; Catalysis; Charge; Chemicals; Complex; Drug Formulations; Electrostatics; Engineering; Enzymes; Excision; Fluorescence Resonance Energy Transfer; Future; Glycopeptides; Glycoproteins; Glycosides; Heart; High temperature of physical object; Hydrophobicity; Intervention; Investigation; Knowledge; Lead; Location; Methods; Micelles; Molecular; Monosaccharides; Non-Steroidal Anti-Inflammatory Agents; Oligopeptides; Organic solvent product; Pharmaceutical Preparations; Plastics; Polymers; Preparation; Proteins; Research; Research Personnel; Shapes; Solubility; Solutions; Structure-Activity Relationship; Techniques; Technology; Testing; Water; aqueous; carboxylate; crosslink; functional group; hydroxyl group; imprint; improved; interest; molecular recognition; monomer; nanoparticle; new technology; novel; protein aminoacid sequence; protein purification; public health relevance; receptor; sensor; sulfa drug; surfactant; tool

 DESCRIPTION (provided by applicant): Molecular recognition is at the heart of biology and many biotechnological applications. If cheap and robust synthetic receptors can be prepared for arbitrarily selected drugs, carbohydrate, or oligopeptides, numerous new technologies and biomedical tools will become possible. Improved drug analysis, extraction of drugs or biomolecules from their natural milieu, novel sensors, intervention of biomolecular recognition, and replacing expensive antibodies in affinity chromatography are but some of the possibilities enabled by such antibody-mimicking materials. Molecular imprinting is a powerful way of making synthetic receptors. Although molecularly imprinted polymers, sometimes referred to as "plastic antibodies", have found applications in chemical and biological sensing, enzyme-like catalysis, and separation, there are significant challenges facing this technology, including heterogeneous binding sites, low percentage of high-affinity binding sites, incomplete template removal, and difficulty in imprinting in water. The overall objective of this proposal is to fill he gap in the knowledge by developing protein-mimicking molecularly imprinted receptors for a broad range of biologically interesting molecules. The proposed molecularly imprinted nanoparticles (MINPs) can be prepared and purified in 2-3 days without any special techniques, as long as the cross- linkable surfactants and other cross-linkers are available. The MINP receptors, typically 3-5 nm in diameter, resemble proteins in size, hydrophilic exterior, and tailored hydrophobic binding pockets in the core, but easily tolerate long-term storage, high temperatures, and organic solvents due to their heavy cross-linking. The proposed research will lead to robust synthetic receptors for a wide range of biologically interesting guests including hydrophobic drugs, carbohydrates, and oligopeptides. Fundamental structure-activity relationship for these biomimetic receptors will be established through the investigation. The research is expected to open up numerous opportunities for chemists, biologists, engineers, and clinicians in the future as cheap "synthetic antibodies" become readily available.

 描述（由申请人提供）：分子识别是生物学和许多生物技术应用的核心。如果可以为任意选择的药物、碳水化合物或寡肽制备廉价而强大的合成受体，那么许多新技术和生物医学工具将成为可能。改进的药物分析、药物或生物分子从其天然环境中的提取、新型传感器、生物分子识别的干预以及在亲和色谱中替换昂贵的抗体只是这些抗体模拟材料所实现的可能性中的一些。 分子印记是制造合成受体的一种有效方法。虽然分子印迹聚合物，有时被称为“塑料抗体”，已发现在化学和生物传感，酶样催化和分离的应用，有重大的挑战，面临这项技术，包括异质结合位点，高亲和力结合位点的百分比低，模板去除不完全，在水中印迹困难。 这项提案的总体目标是填补知识的空白，开发蛋白质模拟分子印迹受体的广泛的生物学感兴趣的分子。所提出的分子印迹纳米颗粒（MINPs）可以在2-3天内制备和纯化，而无需任何特殊技术，只要交联表面活性剂和其他交联剂可用。MINP受体的直径通常为3-5 nm，大小类似于蛋白质，亲水性外部和核心中的定制疏水结合口袋，但由于其重交联而易于耐受长期储存、高温和有机溶剂。 拟议的研究将导致强大的合成受体的广泛的生物学感兴趣的客人，包括疏水性药物，碳水化合物和寡肽。通过这些研究，将建立这些仿生受体的基本构效关系。随着廉价的“合成抗体”变得容易获得，这项研究有望为化学家、生物学家、工程师和临床医生开辟无数的机会。