Generating phosphobodies to activated protein kinases - post-translational modifications (ptms), including phosphorylation, methylation, and acetylation, play a crucial role in cellular biology and…

Generating phosphobodies to activated protein kinases - post-translational modifications (ptms), including phosphorylation, methylation, and acetylation, play a crucial role in cellular biology and diseases. Unfortunately, the tools for selectively monitoring ptms in vivo and in vitro are scarce. Antibodies have often been powerful tools for basic PTM research and clinical testing because they can detect proteins of interest from complex mixtures with reasonable affinity (NM range). However, many antibodies raised to phosphorylated peptides to monitor specific phosphorylation events are animal-derived and lack renewability and protein engineering. Furthermore, some polyclonal antibodies also bind to the non-phosphorylated form of the protein, leading to misinterpretation of results. Tango biosciences offers a unique solution to the challenges above by generating a revolutionary recombinant antibody mimic library that is selective to phosphorylated sites on proteins. This approach has been validated in our successful proof of concept phase i sbir (1 R43 GM146514-01), where we demonstrated outstanding selectivity of our phosphobodies against 53BP1, a protein involved in DNA damage repair. Our initial focus will be expanding our extensive, diverse phosphobody library to include more opportunities to discover binders to 10 activated human protein kinases. The most selective reagents will be sequenced, permitting renewability and expression as recombinant proteins. The work will be accomplished at tango biosciences over two years with the help of two consultants. The achievement of the proposed objectives will enable tango biosciences to advance our client's biology with their drug discovery programs by producing world-class recombinant affinity reagents. IT is expected that the technical advances here will not only attract new service contracts but also establish tango biosciences as a true innovator in monitoring phosphorylation with exquisitely selective affinity reagents, which may advance biomedical science and potentially lead to new therapeutic opportunities.