Synthesis and Study of Inhibitors of Ubiquitin Ligases

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

This project aims to complete a total synthesis of a recently isolated natural product. We aim to complete the synthesis in a minimum number of steps, while developing a flexible route that will enable the production of significant quantities of the natural product. Furthermore, this work will enable access to analogs and model compounds that will enable the understanding of structure-activity relationships, as well as the mode of binding to the ligase. For example, we believe that this molecule may be a cysteine-reactive compound. A total synthesis effort will enable us to generate deletion analogs lacking specific functional groups, as well as biotinylated or fluorescent affinity/imaging probes that will be critical for understanding the molecular mechanism of action. We have made significant progress toward completing the synthesis, and plan to make contributions to the biology side of this project in the near future.