Application:
- Redox regulation is comparable to protein modifications like phosphorylation and dephosphorylation in its ability to rapidly modulate protein and cellular function.
- It is mediated by the reversible thiol oxidation of highly reactive cysteine residues that can play structurally and/or functionally important roles in cells and tissues.
- Despite its importance, only a limited set of tools is available to identify and quantify redox-sensitive sites within cellular proteomes. The majority of existing tools are able to quantify global changes in the redox status of cells or in protein thiol groups, with a poor ability to identify specific redox-regulating sites within proteins and monitor changes in their oxidation.
- These redox-regulating proteins define healthy cellular physiology, aging, and serve as markers for diverse pathologies such as cancer, neurodegenerative diseases, diabetes, and more. Since cysteines account for ~10% of the residues in proteins, one of the main challenges in redox proteomics is to capture and isolate thiol-containing protein fragments, while minimizing non-specific oxidation induced during sample preparation and by the mass spectrometer itself.
Our innovation:
We develop an innovative approach to detect, quantify, and monitor changes in redox-sensitive cysteines among complex proteomes.
We design and synthesize a set of reagents, which specifically interact with reduced cysteine thiols, which are used to derive a platform for redox proteomics in cells, focusing on monitoring changes in oxidation during cell proliferation and aging. Those reagents can be used to identify biomarkers based on a protein oxidation profile in disease-related samples (such as cancer and neurodegenerative diseases).
Our goal is to bring to the market a set of products, as research and diagnostic tools enabling mapping and quantitative analysis of protein oxidation in cells and tissues.
Advantages:
- Novel designed reagents based on a simple peptide sequence, which can have multiple versions for modifications, increasing the number of differential thiol-trapping reagents that can be used in one MS analysis.
- Incorporation of a unique cleavage site that removes the enrichment tag prior to or during the MS run, without any need for additional purification steps.
- Significant reduction in the complexity of sample preparation, saving material and time (days!).
Opportunity:
Our reagents will be used to establish an advanced proteomic platform to perform quantitative and multiplexing redox proteomics that can be applied to a wide range of biological and therapeutic applications. Today, thiol-alkylating and proteomics-oriented reagents have a valuable place in the catalogs of all major chemical, life sciences, and biotechnology companies.
Moreover, we provide a new strategy to design differentially different labeling probes that can be used in a global proteomic pipeline, as well as in other areas of life science research, including cell biology, biochemistry, and others.
