Epitope-targeted peptide inhibitors of Myc-Max Dimerization

Myc is a popular transcription factor that is found in about 30% of human cancers. Along with being present in many cancers, it is also a potent oncogenic driver. Myc dimerizes with Max in order to promote transcription of genes that are associated with cellular proliferation, differentiation, and survival. In cancers that are Myc-driven, the Myc concentrations are higher than in healthy cells. Developing drugs in which impede Myc-Max dimerization has been difficult because there are many interactions that occur over large interfaces. This project hypothesizes that using molecular peptide ligands that adsorb to Myc at the Myc-Max dimer interface will disrupt the intermolecular interactions between Myc-Max. Molecular screening is used to identify cyclic peptide ligands that will have a high binding affinity to epitopes on Myc. By using the peptide ligands, they can be tested to measure their affinity to the Mac protein, the location of the binding on Myc, and its ability to inhibit the formation of the dimer by Myc-Max. By having this data, it then can be used to engineer peptides that are potent inhibitors of Myc-Max dimerization