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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）：碳水化合物官能化的纳米颗粒，即，糖纳米颗粒具有广泛的应用，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、癌症诊断到疫苗发现。然而，与DNA和蛋白质功能化纳米粒子相比，糖基纳米粒子的发展却远远落后。目前，通过将硫醇修饰的碳水化合物缀合到纳米颗粒表面上来制备糖纳米颗粒的报道非常少。然而，硫醇改性的碳水化合物的制备需要多步合成操作，这是困难和耗时的。目前，没有可商购的用于科学和生物医学研究团体的缀合试剂盒来简单地将碳水化合物探针缀合到纳米颗粒表面上。在这个NIH SBIR项目中，ADA Technologies Inc.将使用我们专有的聚糖表面缀合化学来开发一种简单而通用的方法，用于将未修饰的碳水化合物和糖蛋白一步到位地缀合到Au和半导体纳米颗粒上。I期项目的具体目标是1）设计和产生作为偶联试剂的双官能树枝化基元配体，其中树枝化基元分子带有用于碳水化合物的多个相同的酰基-酰肼偶联点和用于附着到金属纳米颗粒表面的巯基; 2）开发和评估微型化微波辐射能量用于在树枝状修饰的纳米颗粒上快速和方便地偶联碳水化合物的用途，并证明制备代表性糖纳米颗粒的可行性; 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，用于结合生物学上重要的碳水化合物，以产生广泛的糖纳米颗粒。缀合试剂盒包括酰肼-树枝化基元配体官能化的纳米颗粒和用于缀合碳水化合物探针的方案。用这种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形状。在第二阶段，我们将通过制备各种各样的碳水化合物探针缀合在具有不同发射波长的纳米晶体上来开发糖纳米粒子库，开发磁性糖纳米粒子用作MRI试剂，并展示糖纳米粒子作为有效的亲和标记和体内细胞标记和成像的用途，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，用于定制具有3D多价碳水化合物显示和球形形状的碳水化合物官能化纳米颗粒（即糖纳米颗粒）。该方法允许制备具有生物学上重要的碳水化合物的糖纳米颗粒。糖纳米颗粒可用作有效的亲和标记物以及用于体内细胞标记和成像。