Direct targeting of intrinsically disordered proteins such as MYC or protein-protein interactions (PPIs)  of remains a challenging issue in chemical biology and medicine. Therefore, we developed gold-based reagents to chemically modify the MYC protein via a covalent bioconjugation of a reactive lysine residue using metal ligand affinity chemistry (MLAC). Chemical biology, cell-based MYC target engagement studies including co- immunoprecipitation, cell viability studies in MYC dependent cells, transcriptional factor assay and biophysical characterization revealed that our gold(I) pharmacophore modulates intracellular MYC activity. This study can be used as a very good premise to target PPIs and expand the scope of metal-based probes to study protein function and as therapeutic agents to treat cancer.

Covalent modification of native c-MYC protein by Au(I) pharmacophore

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.