Methods And Compositions For Modifying Transcription Factor Activity by Targeting The Human Mediator Complex Using Cell Penetrating Memetic Peptides And Methods of Treating Cancer Using The Same

摘要

The invention includes novel systems, methods, and compositions to inhibit TF function by disrupting the TF-Mediator interaction. In this preferred aspect, functional mimics of TF activation domains may be rationally designed to block TF-Mediator binding and selectively inhibited TF-dependent transcription and may further incorporate a penta-arg motif for enhanced cell penetration. In one preferred embodiment of the invention novel stapled mimetic peptides of p53 activation domains incorporating a penta-arg motif were rationally designed to block p53 function by disrupting the p53-Mediator interaction. Additional aspects of the invention include methods of treating cancer in a subject, and other diseases related to the activity of the TFs, such as p53, and the Mediator complex, and its downstream TF-dependent transcription.