Insights on AApeptides as they relate to Inhibiting the p300 CH1 domain

The HIF-1 pathway helps sustain cancerous tumors by preventing tumor cells from becoming necrotic. The histone acetyltransferase p300 protein is a vital coactivator used in the HIF-1 (hypoxia inducible factor) pathway by binding to subunit HIF-1a. Within our lab we aim to use novel AApeptides as a means of competitively inhibiting the p300 coactivator from binding to the HIF-1a subunit. In order to do this we are specifically studying the protein protein interactions of the CH1 (cysteine/histidine rich-1) domain of the p300 protein as it binds to the C-terminal transactivation domain of the HIF-1a subunit. The p300 CH1 domain is purified through detergent-solubilization followed by incubation with Ni-NTA resin. The supernatant is then purified via IMAC purification using Ni-NTA resin and an imidazole wash. Reverse IMAC is thereafter used to remove the His tag from p300 CH1 domain. The concentrated protein is then analyzed in SDS PAGE. In the future we hope to find AApeptides that can competitively inhibit the p300 proteins with a strong binding affinity. With promising results, this line of research is a testament for the myriad of practical applications that can come from AApeptides and peptidomimetics in general. On top of this, this line of research could also provide a new method to fight cancer.