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

基本信息

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
项目类别：
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

项目摘要

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且强大的合成受体，则许多新技术和生物医学工具的改进将成为可能。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取代亲和层析中昂贵的抗体只是此类技术所实现的一些可能性分子印迹是制造合成受体的有效方法，尽管分子印迹聚合物（有时称为“塑料抗体”）已在化学和生物传感、类酶催化和分离中得到应用。该技术面临的挑战，包括异质结合位点、高亲和力结合位点比例低、模板去除不完全以及在水中印迹的困难。该提案的总体目标是通过开发来填补知识空白。所提出的分子印迹纳米粒子（MINP）可以在 2-3 天内制备和纯化，无需任何特殊技术，只要可交联的表面活性剂和其他交联剂即可。 MINP 受体直径通常为 3-5 nm，蛋白质大小相似，外部具有亲水性，核心具有定制的疏水性结合袋，但易于长期储存，由于其重交联，因此能够耐受高温和有机溶剂。拟议的研究将针对一系列具有生物学意义的客体（包括疏水性药物、碳水化合物和寡肽）产生强大的合成受体。随着廉价的“合成抗体”变得容易获得，这项研究预计将在未来为化学家、生物学家、工程师和大众带来大量的机会。