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Magneto-optical Technology for Screening Receptor Libraries

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
94097
Program Year/Program:
2009 / SBIR
Agency Tracking Number:
RR025724
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
Radiation Monitoring Devices, Inc.
44 Hunt St. Watertown, MA 02472-
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2009
Title: Magneto-optical Technology for Screening Receptor Libraries
Agency: HHS
Contract: 1R43RR025724-01
Award Amount: $180,001.00
 

Abstract:

DESCRIPTION (provided by applicant): Radiation Monitoring Devices, Inc. (RMD) proposes to develop a platform technology and device capable of high throughput screening of the association between biologically/pharmacologically active molecules and their cog nate receptors. RMD has demonstrated that maghemite nanoparticles, decorated with antibodies, exhibit longer magnetic birefringence relaxation times when associated with viruses and small size microorganisms. The absolute magnitude of birefringence and the relaxation time depends only on the hydrodynamic volume change upon formation of the receptor-ligand complex, and is not affected by excess unbound ligand. These properties make this assay ideal for screening molecules immobilized on the surface of magn etic nanoparticles against receptors, receptor libraries and mutant receptor libraries. We propose to develop the above observation into a high throughput assay platform to detect an association between small molecule ligands and cognate receptors. We will demonstrate the proof of concept by monitoring the change in magnetic birefringence relaxation upon binding of a nanoparticle-immobilized small molecule to 2-adrenergic receptors overexpressed on the cell surface of microorganisms, such as bacteria and ye ast. The rationale for using magneto-optical birefringence to identify ligand and receptor interactions is that it eliminates the need for separating the unbound ligands from ligands captured by receptors. The time to identification is reduced since there is no need to segregate sample from the capture particle before detection. Importantly, attachment of an exogenous fluorescent or radioactive label to the receptor or ligand is not required. Further, this novel approach is applicable in systems where the i nteraction of ligand with cognate receptor does not activate intracellular pathways that are easy to monitor with a ratiofluorometric platform. This procedure/device will be useful for a broad range of applications in the pharmaceutical/biotechnological in dustry, including discovery research to develop small molecule drugs, and the identification of biologically active peptides and proteins from display libraries. Another application is the identification of orphan receptors, and discovery of receptors for ligands of interest. This approach will also be useful for aspects of basic research, such as mapping and deciphering the ligand binding pocket for a number of cognate receptors for applications in rational drug design. PUBLIC HEALTH RELEVANCE: This propos al solicits funding for developing a high-throughput platform to detect an association between magnetic nanoparticle-immobilized ligand molecules and a vast array of receptors. The technology can be utilized for a fast and accurate determination of ligand- receptor association, and will have a broad range of applications in the pharmaceutical/biotechnological industry, including discovery research to develop small molecule drugs, and the identification of biologically active peptides and proteins from displa y libraries. This approach will also be useful for aspects of basic research, such as mapping and deciphering the ligand binding pocket of receptors for applications in rational drug design.

Principal Investigator:

Gyula Varadi
5136686863
GVARADI@RMDINC.COM

Business Contact:

Gerald Entine
gentine@rmdinc.com
Small Business Information at Submission:

RADIATION MONITORING DEVICES, INC.
44 Hunt Street WATERTOWN, MA 02472

EIN/Tax ID: 042546395
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No