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: 9531389
• 负责人: Yan Zhao
• 金额: $ 25.19万
• 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 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9531389
• 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; Heart; High temperature of physical object; Hydrophobicity; Intervention; Investigation; Knowledge; 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; hydrophilicity; hydroxyl group; imprint; improved; molecular recognition; molecular size; monomer; nanoparticle; new technology; novel; protein aminoacid sequence; protein purification; public health relevance; 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(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，许多新技术和生物医学工具将成为可能。改进药物分析，从自然环境中提取药物或生物分子，新型传感器，生物分子识别的干预，以及在亲和层析中取代昂贵的抗体，这些只是这种抗体模拟材料实现的一些可能性。分子印迹是制造合成受体的一种有效方法。尽管分子印迹聚合物，有时被称为“塑料抗体”，已经在化学和生物传感、酶类催化和分离方面得到了应用，但这项技术面临着巨大的挑战，包括结合位点的异质性、高亲和力结合位点的比例低、模板去除不完全以及在水中难以印迹。这项提议的总体目标是通过为广泛的生物感兴趣分子开发模仿蛋白质的分子印迹受体来填补这一知识空白。只要有可交联型表面活性剂和其他交联剂，分子印迹纳米粒子(MINP)可以在2-3天内制备和纯化，而不需要任何特殊的技术。MINP受体的直径通常为3-5 nm，在大小上类似于蛋白质，表面亲水性强，核心部分有量身定制的疏水结合袋，但由于其高度的交联性，很容易耐受长期储存、高温和有机溶剂。这项拟议的研究将为包括疏水药物、碳水化合物和寡肽在内的广泛的生物有趣的客体带来强大的合成受体。通过研究，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”随处可得，这项研究有望在未来为化学家、生物学家、工程师和临床医生打开无数机会。