Nadya I. Tarasova, Ph.D.

The use of chemical biology tools for studying protein functions has many advantages over applications of genetic approaches, such as gene knockouts shRNAs and siRNAs, particularly for multifunctional proteins. Chemical probes allow for interrogation of a subset of protein-protein interactions rather than eliminating all functions of the protein under study. Consequently, they are instrumental in uncovering detailed mechanisms of protein function that include feedback loops and autoinhibition. Chemical probes also provide for more efficient translation of findings into the clinic because many of them represent drug leads. However, the wide use of chemical probes is hampered by difficulties in their generation and characterization.  Therefore, SBF develops new technologies that simplify and accelerate identification, generation and characterization of chemical probes. Three approaches for identification of binders are used depending on the target: 1) Virtual screening of large libraries of Synthetically Accessible Virtual Inventory (SAVI); 2) Self-assembling  peptide antagonists of integral membrane proteins that form fully synthetic virus-like particles and thus are able to deliver themselves effectively in vivo; 3) Cell-permeable peptidomimetics with rigid and predictable structures amendable to rational drug design.

External funding of the projects includes: CDMRP Prostate Cancer Research Award PC08116 'Self-assembling peptide nanoparticles targeting prostate tumors' and CRADA with Oncolinx Pharmaceuticals “Pre-clinical Development of Azonafide-based Antibody Drug Conjugates”.