SBIR-STTR Award

Our goal under this SBIR is to demonstrate the feasibility of using a novel Artificial Sequence-based Protein REceptor (ASPIRE) for the creation of a "protein chip." The development of new protein separation technology is essential to bridge the gap between genomics and rational disease diagnostics and treatment. Preliminary results indicate that we can design an artificial receptor, based solely on the predicted protein sequence, capable of purifying a target protein from a cell lysate. To prove that such a receptor will be useful for large-scale high-throughput proteome separation and analysis, we plan to 1) demonstrate that the technology is applicable to 6-10 representative proof of principle proteins; 2) optimize the critical receptor properties for efficient separation of complex samples; and 3) create an array of receptors capable of separating labeled proteins. Our data indicate that a chip based on the ASPIRE technology will be roughly 250x faster and lOx more sensitive than two-dimensional gel electrophoresis paired with mass spectrometry. In addition to the analysis of protein expression patterns, ASPIRE protein chips will allow researchers to conduct large-scale parallel analysis of posttranslational modifications and intracellular trafficking control much of cell regulation. We expect that this technology will have far-reaching implications for basic research, drug development, and disease diagnosis. PROPOSED COMMERCIAL APPLICATION: The market for proteomics is estimated at $4 billion and is rapidly growing. A protein chip enabling proteomics would allow for 1) rapid identification of molecular causes of disease and therapeutic targets 2) efficient screening of small molecules for therapeutic efficacy and toxicity, and 3) rational diagnostic and treatment strategies based on individual molecular profiling.

Our goal under this Phase II SBIR is to demonstrate that Protein Print TM Arrays can be effectively used for parallel expression profiling of biomarkers and novel therapeutic targets. As part of this work we will generate a commercially viable biomarker array for cancer research and diagnostics and optimize binding and detection conditions. During Phase I, we successfully generated arrays against six proof-of-principle proteins with diverse functions and properties. The cavities have high affinities (Kd ~ l nM) comparable to very good antibodies and specificity at the single amino acid level. This technology represents a breakthrough in our ability to study novel proteins with the potential to resolve the bottleneck in converting the wealth of genomic information into improved drug discovery.

Thesaurus Terms:
chemical structure function, intermolecular interaction, microarray technology, protein purification, protein sequence, proteomics, receptor, technology /technique development acidity /alkalinity, gene expression, high throughput technology, informatics, intracellular transport, molecular shape, polymer, posttranslational modification, protein quantitation /detection bioengineering /biomedical engineering, biotechnology, crosslink, fluorescence spectrometry, fluorescent dye /probe, peptide chemical synthesis