SBIR Phase I: New ABPP Probes and Sample Preparation Methods for Biomarker Discoveries

This Small Business Innovation Research (SBIR) Phase I project aims to address a key challenge facing modern proteomics - identification and quantification of low abundant biologically functional proteins in small size, dilute and/or archived samples using mass spectrometry (MS)-based analysis. A combined use of novel chemical biology and sample preparation strategies is proposed to tackle this challenge. The set of specific reagents to be developed composes specific Activity Based Protein Profiling (ABPP) probes, cleavable high affinity solid support conjugation for quantitative target enrichment, and stable isotopic labels for MS identification and quantification. An enabling sample preparation method employed prior to the MS analysis will also be optimized for the ABPP probe labeling. At the completion of the project, including a Phase II study on broader ABPP labeling applications, commercial kits will be made available for life science laboratories that conduct proteomic studies. The broader impacts of this research are, 1) it is a major step forward in advancing MS-based proteomic studies and biomarker discoveries based on functional low abundance proteins found in small size biospecimen; and 2) the successful commercialization of this technology and associated products will expand the breadth of possible studies using ABPP based quantitative proteomics. The technological and societal benefits of these products will become apparent, when these products enable new biomarkers discoveries, and the newly identified biomarkers are used in addressing fundamental biological questions, accelerating the development of new clinical diagnostic tests and new therapeutic agents.