Chemistry Student Seminar: Stephanie Jayne

Abstract

Pretty keen for a protein: developing inhibitors for the Tec SH3 domain

Protein-protein interactions (PPIs) have been implicated in the progression of many diseases and are considered highly attractive therapeutic targets, but the development of drug-like small-molecule inhibitors has been slow due to the intrinsic challenges of the protein targets. 

Using a structure-based ligand design approach, derivatives of 2-aminoquinoline had previously been found to bind to the target murine Tec SH3 domain with promising indications that a more strongly binding ligand could be developed.

In this project, a range of novel 2-aminoquinoline compounds with potential to bind to the SH3 domain were designed and procedures were developed for their synthesis, resulting in the most effective small molecule ligands for the SH3 domain to date.

The challenges of targeting the SH3 domain and the strategies employed in this project to develop more effective inhibitors will be described, with the results demonstrating the potential of small molecules as therapeutics for PPI domains.