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Abstract
Grant Number: 1R43GM081972-01 Project Title: Conjugation Kits for Facile Preparation of Multivalent Glyco-nanoparticles
PI Information: Name Title ZHOU, XICHUN xichunz@adatech.com SR. RESEARCH SCIENTIST Abstract: 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.
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Institution: ADA TECHNOLOGIES, INC. 8100 SHAFFER PKWY, STE 130 LITTLETON, CO 80127 Fiscal Year: 2007 Department: Project Start: 01-SEP-2007 Project End: 29-FEB-2008 ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES IRG: ZRG1