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Conjugation Kits for Facile Preparation of Multivalent Glyco-nanoparticles

用于轻松制备多价糖纳米颗粒的缀合试剂盒

基本信息

批准号：
7326631
负责人：
XICHUN ZHOU
金额：
$ 9.99万
依托单位：
ADA TECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7326631
关键词：
Affinity Affinity Labels Amines Anti-Adhesion Agent Antibodies Antigens Area Binding Biochemistry Biological Biological Assay Biology Biomedical Research Biosensor Biotechnology Budgets Cancer Diagnostics Carbohydrates Cell surface Chemical Engineering Chemistry Class Collaborations Communities Complex Condition Consult Consultations Coupled Coupling Crosslinker DNA Dendrimers Detection Development Diagnosis Diagnostic Disaccharides Drug Delivery Systems Ensure Florida Fucose Generic Drugs Glycobiology Glycol Glycols Glycoproteins Gold Image Immobilization Immunoassay Immunology Individual Information Storage Investigation Label Laboratories Laboratory Technicians Lectin Left Libraries Ligands Magnetic Resonance Imaging Magnetism Mannans Medical Methodology Methods Modeling Modification Molecular Monosaccharides NMR Spectroscopy Nanotechnology Nucleic Acids Oligonucleotides Oligosaccharides One-Step dentin bonding system Organic Chemistry Organic Synthesis Outcome Oximes Partner in relationship Phase Physical condensation Polysaccharides Preparation Principal Investigator Process Protein Microchips Protein-Carbohydrate Interaction Proteins Proteomics Protocols documentation Qualifying Quantum Dots Radiation Range Reagent Reporting Research Schedule Scheme Science Scientist Screening procedure Semiconductors Shapes Signal Transduction Silicon Dioxide Site Small Business Funding Mechanisms Small Business Innovation Research Grant Source Spectrum Analysis Sulfhydryl Compounds Surface System Techniques Technology Therapeutic Therapeutic Agents Time Transmission Electron Microscopy United States National Institutes of Health Universities Ursidae Family Vaccines Water Work affinity labeling antibody conjugate base cellular imaging design experience immunogenic in vivo interest medical schools microwave electromagnetic radiation mimetics miniaturize nanocrystal nanomaterials nanoparticle nanosensors professor receptor self assembly success tool vaccine development

项目摘要

DESCRIPTION (provided by applicant): Carbohydrate functionalized nanoparticles, i.e., the glyco-nanoparticles, have wide application ranging from studies of carbohydrate-protein interactions, in vivo cell imaging, biolabeling, cancer diagnostics, and to vaccine discovery. However, in comparison with DNA and protein functionalized nanoparticles, the development of glyco-nanoparticle has been left far behind. Currently the very few reported glyconanoparticles were prepared by conjugating thiol modified carbohydrates onto nanoparticle surfaces. However, the preparation of thiol modified carbohydrates required multi-step synthetic manipulations which are difficult and time consuming. Currently, there are no conjugation kits that are commercially available for scientific and biomedical research communities to simply conjugate carbohydrate probes onto nanoparticle surface. In this NIH SBIR project ADA Technologies Inc. will use our proprietary glycan surface conjugation chemistry to develop a simple and versatile method for one-step, site-specific conjugation of unmodified carbohydrates and glycoprotein onto Au and semiconductor nanoparticles. The specific aims of the Phase I project are 1) to design and generate a bi-functional dendron ligand as a coupling reagent where the dendron molecule bears multiple identical acyl-hydrazide coupling points for carbohydrates and a sulfhydryl for attachment to the metallic nanoparticle surface; 2) to develop and evaluate the use of miniaturized microwave radiation energy for quick and convenient coupling carbohydrates on the dendron-modified nanoparticles, and demonstrate the feasibility of preparing representative glyconanoparticles; 3) to characterize the glyco-nanoparticles and verify the immunogenic activities of the glyconanoparticles. The success of the phase I project will provide the scientific and biomedical research communities with a set of kits for conjugating biologically significant carbohydrates to generate a wide range of glyco-nanoparticles. The conjugating kits include the hydrazide-dendron ligand functionalized nanoparticles and protocols for conjugation carbohydrate probes. The glyconanoparticles prepared with this technology will have 3D polyvalent carbohydrate display, with globular shapes that are suitable for probing carbohydrate-protein interaction. In Phase II, we will develop a glyconanoparticle library by preparing a wide range of carbohydrate probes conjugated on nanocrystals with different emission wavelengths, develop magnetic glyconanoparticles for use as MRI reagents, and demonstrate the use of glyconanoparticles as an efficient affinity label and in vivo cellular labeling and imaging, and develop a full operational protocol for end-users. A simple and versatile methodology is proposed for tailoring carbohydrate-functionalized nanoparticles (i.e. glyconanoparticles) with 3D polyvalent carbohydrate display and globular shapes. This methodology allows the preparation of glyconanoparticles with biologically significant carbohydrates. The glyconanoparticles can be used as efficient affinity labels as well as for in vivo cellular labeling and imaging.

描述（由申请人提供）：碳水化合物功能化纳米颗粒，即糖纳米颗粒，具有广泛的应用范围，从碳水化合物-蛋白质相互作用的研究，体内细胞成像，生物标记，癌症诊断和疫苗发现。然而，与DNA和蛋白质功能化纳米颗粒相比，糖纳米颗粒的发展还远远落后。目前很少报道的糖聚糖颗粒是通过将硫醇修饰的碳水化合物偶联到纳米颗粒表面来制备的。然而，巯基改性碳水化合物的制备需要多步合成操作，既困难又耗时。目前，还没有商业上可用于科学和生物医学研究界的偶联试剂盒来简单地将碳水化合物探针偶联到纳米颗粒表面。在这个NIH SBIR项目中，ADA技术公司将使用我们专有的聚糖表面偶联化学来开发一种简单通用的一步法，将未修饰的碳水化合物和糖蛋白偶联到Au和半导体纳米颗粒上。一期项目的具体目标是：1)设计并生成一种双功能的树突配体作为偶联剂，其中树突分子具有多个相同的碳水化合物酰基酰肼偶联点和一个巯基，用于附着在金属纳米颗粒表面；2)开发和评价利用小型化微波辐射能在树突修饰纳米粒子上快速方便地偶联碳水化合物，并论证制备代表性糖聚糖颗粒的可行性；3)表征糖纳米颗粒并验证糖纳米颗粒的免疫原性活性。第一阶段项目的成功将为科学和生物医学研究界提供一套试剂盒，用于结合具有生物学意义的碳水化合物，以产生广泛的糖纳米颗粒。偶联试剂盒包括肼-树突配体功能化纳米颗粒和偶联碳水化合物探针的方案。用该技术制备的糖纳米颗粒将具有3D多价碳水化合物显示，具有适合探测碳水化合物-蛋白质相互作用的球形。在第二阶段，我们将通过制备具有不同发射波长的纳米晶体上的各种碳水化合物探针来开发糖聚糖颗粒库，开发用于MRI试剂的磁性糖聚糖颗粒，并演示糖聚糖颗粒作为有效亲和力标记和体内细胞标记和成像的使用，并为最终用户开发完整的操作方案。提出了一种简单而通用的方法，用于剪裁具有三维多价碳水化合物显示和球形的碳水化合物功能化纳米颗粒（即糖纳米颗粒）。该方法允许制备具有生物意义的碳水化合物的糖聚糖颗粒。糖聚糖颗粒可以用作有效的亲和标记以及体内细胞标记和成像。