Target Identification: Methodology Development and a Case Study

Abstract

Accurate characterization of small molecule-protein interactions is one of the most important but very challenging tasks in chemical, biological, and pharmaceutical sciences. In the first part of the presentation, we will describe a novel affinity labeling method named DNA-programmed Photo-Affinity Labeling (DPAL). DPAL’s unique dual-probe system provides simple, flexible and modular affinity labeling of small molecule’s protein targets. Importantly, the introduction of DNA tags enables multiplexed protein labeling. We will describe the methodology development and its recent extension to studying DNA-protein interactions. In the second part, we will report a target identification project we recently completed. Terazosin, a marketed anti-hypertension drug, exhibits anti-apoptosis and protective activities in septic mouse. We have identified terazosin’s new target of pgk-1 and elucidated the molecular mechanism underlying its new biological activities.