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Abstract
Grant Number: 1R43DK062593-01A1 PI Name: ZEBALA, JOHN A. PI Email: PI Title: CHIEF TECHNICAL OFFICER Project Title: Meta-Molding Arrays Abstract: DESCRIPTION (provided by applicant): Protein chips offer the potential to profile the levels and kinetics of proteins in tissues of the digestive and endocrine systems in a highly multiplexed format. Despite this potential, the majority of protein chips are based on arrayed bio-molecules obtained from biologic or enzymatic sources. Chips that rely on biology or enzymes suffer from several inherent shortcomings that include a restricted bio-molecule repertoire that is time-consuming and costly to manufacture, especially at high-density. We propose to overcome these limitations by developing a Meta-Molding array technology that consists of arrays of novel synthetic antibody mimetics. Mimetics will be identified using a novel and purely chemical discovery paradigm termed PNAdisplay. Consistent with previous studies in the field of dynamic combinatorial chemistry, we hypothesize that PNA-display will permit us to screen large heterodimer populations and identify at least moderate affinity mimetics in a facile system (i. e. < 10 (M). Arrays of such moderate-affinity mimetics employed with an orthogonal analytical method such as MALDI-TOF will provide an analytical capability exceeding that of antibody arrays alone, but without the disadvantages. This SBIR Phase I proposal is designed to prove the feasibility of using PNA-display to identify at least moderate affinity mimetics. Feasibility will set the stage to move into an aggressive Phase II program to develop a Meta-Molding array that monitors global intracellular signaling by detecting specific phosphopeptides. Inappropriate intracellular phosphorylation results in several diseases, including cancer, non-insulin dependent diabetes, and peripheral neuropathies. Syntrix will commercialize the Meta-Molding arrays that result from this research through third-party joint ventures.
Thesaurus Terms:
antibody, biomimetics, microarray technology, protein quantitation /detection, synthetic protein, technology /technique development
biological signal transduction, intracellular, matrix assisted laser desorption ionization, phosphopeptide
biotechnology
Institution: SYNTRIX BIOSYSTEMS, INC. BOX 166, 16625 REDMOND WAY NE, STE M REDMOND, WA 98052 Fiscal Year: 2003 Department: Project Start: 01-SEP-2003 Project End: 31-AUG-2005 ICD: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES IRG: ZRG1
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