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Abstract

Grant Number:	5R21CA093287-02
Project Title:	Development of Protein-Detecting Microarrays

PI Information:	Name	Email	Title
	KODADEK, THOMAS J.	kodadek@scripps.edu	PROFESSOR

Abstract: DESCRIPTION: (provided by applicant) This project is directed towards the development of protein-detecting micro arrays (PDMs) that will allow the sensitive and quantitative analysis of hundreds or, eventually, thousands of proteins simultaneously. A major obstacle to development of PDMs is the formidable task of isolating and producing in quantity so many different protein-binding agents. It is argued here that while the first generation of such devices will employ antibodies or other macromolecules with antibody-like binding properties, in the long run synthetic protein ligands would be preferred greatly. These could be made more easily and in far larger quantities than biomacromolecules, a critical issue if this technology is to be adopted broadly. A straightforward method to isolate "pincer ligands" is proposed. These are readily synthesizable molecules consisting of a lead peptide, isolated by phage display, coupled to another peptide or peptide-like compound. These species are anticipated to bind tightly to their target proteins via two point contacts or clamp-like interactions. A novel approach to the high-throughput isolation of such compounds is proposed that obviates many of the problems inherent in current methods used to obtain such ligands. A second issue of critical importance will be to develop methods suitable for monitoring, in a sensitive and quantitative fashion, binding of the proteins in a biological sample to the various capture ligands on the array. We propose a novel magnetic resonance imaging (MRI)-based method to accomplish this task without the need to chemically label the proteins in the sample. Demonstrating the feasibility of these approaches to solving the two most serious roadblocks to the development of PDMs will constitute the R21 phase of this project. If successful, we will then move to apply these technologies to the creation and evaluation of functional PDMs.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
biomedical equipment development, microarray technology
binding protein, fluorescent dye /probe, ligand, protein protein interaction
magnetic resonance imaging

Institution:	UNIVERSITY OF TEXAS SW MED CTR/DALLAS
	DALLAS, TX 753909105
Fiscal Year:	2002
Department:	INTERNAL MEDICINE
Project Start:	28-SEP-2001
Project End:	31-AUG-2004
ICD:	NATIONAL CANCER INSTITUTE
IRG:	ZCA1

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