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: 9117561
• 负责人: Yan Zhao
• 金额: $ 24.09万
• 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/9117561
• 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; Electrostatics; Engineering; Enzymes; Excision; Fluorescence Resonance Energy Transfer; Formulation; Future; Glycopeptides; Glycoproteins; Glycosides; Health; 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; Polymers; Preparation; Proteins; Research; Research Personnel; Shapes; Solubility; 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; receptor; sensor; sulfa drug; surfactant; synthetic antibodies; 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（应用程序提供）：分子识别是生物学的核心和许多生物技术应用。如果可以为任意选择的药物，碳水化合物或寡肽准备便宜且健壮的合成受体，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，从天然环境中提取药物或生物医学工具的提取，新型传感器，生物医学识别的干预措施以及替代亲和色谱中昂贵的抗体，但这种模仿材料的可能性是某些可能性。分子烙印是制造合成受体的强大方法。尽管有时被称为“塑料抗体”的分子印迹聚合物在化学和生物学敏感性，酶样催化和分离中发现了应用，但这种技术面临的巨大挑战，包括异质性结合位点，低比例的高度结合位点的低比例，不完整的模拟模板和较难的水分，在Inflate and Impinting中，在Inflate and Impinting in in Impints中。该提议的总体目的是通过为广泛的生物学有趣分子开发模仿蛋白质的分子添加受体来填补知识的空白。只要可以提供可用的交叉链接表面活性剂和其他交叉链接器，就可以在2-3天内制备和纯化所提出的分子不张纸纳米颗粒（MINP）。 MINP受体通常直径为3-5 nm，类似于大小，亲水性外部和核心中量身定制的疏水结合口袋，但由于其重型交叉连接而易于耐受长期存储，高温和有机溶液。拟议的研究将导致广泛的生物学有趣的客人（包括疏水药物，碳氢化物和寡肽）的众多合成受体。这些仿生受体的基本结构活性关系将通过研究建立。预计这项研究将在未来为化学家，生物学家，工程师和临床医生提供众多机会，因为便宜的“合成抗体”很容易获得。