Molecule-Guided Investigations into p53 Biology

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

The setup of the Bernal Laboratory began in May of 2010. Over the course of the last few months, we have been dedicating our time to build the infrastructure of the laboratory. Now that the renovations and construction of the lab space has been completed and most of the equipment has been installed, we are poised to embark in the investigations outlined above. The work in this project is multi-disciplinary, and it comprises a mixture of synthetic chemistry, biochemistry, molecular biology and cell biology. With the recent installation of a peptide synthesizer and a liquid chromatography mass spectrometry (LC/MS) system in my laboratory, we are prepared to design, synthesize and purify the stapled peptides that we will use in our biological studies. We currently aim to construct compounds that include the murine variants of SAH-p53 (see Goals section), modulators of RING domain interactions in proteins involved in ubiquitylation, and peptides that block the activation function and coactivator binding site of nuclear receptors. On the biology front, we will be well-positioned to study in-house all of the molecules that we will synthesize in the laboratory. We will explore the biochemical and biophysical properties of the compounds and test their behavior in protein binding assays. Their activity will be assessed using both recombinant proteins and a wide array of cancer cell lines.