Albert Bowers, Ph.D., has received a R35 Outstanding Investigator Award worth more than $1.9 million over five years from the National Institute of General Medical Sciences to study the chemoenzymatic synthesis, mode of action and evolution of natural product-based macrocycles.
Bowers is an assistant professor in the School’s Division of Chemical Biology and Medicinal Chemistry. He is a member of the UNC Lineberger Comprehensive Cancer Center and affiliate member of the Center for Integrative Chemical Biology and Drug Discovery.
“Natural peptide macrocycles are promising next-generation therapeutics, due to their abilities to bind to challenging protein targets, such as protein interfaces and transcription factors,” Bowers said. “The goal of our lab is to use insights and chemistries from natural product biosynthesis to facilitate the discovery and development of new natural-product-like peptide macrocycles. We will use a combined chemical and enzymatic approach for synthesis of highly constrained peptide macrocycles similar to those used in nature.”
Over the next five years, Bowers said he will divide his team’s efforts among three project areas:
- They will develop a chemoenzymatic platform for the preparation of analogs of the thiopeptide natural products and use the platform to examine new, diversity-generating enzymes from complimentary ribosomal natural product pathways.
- They will investigate the multifaceted biological activities of thiopeptides and develop potent and selective inhibitors of the oncogenic transcription factor FoxM1. A major thrust of this research will be structure elucidation of thiopeptides bound to FoxM1.
- They will combine enzymes from ribosomal peptide natural product with mRNA display to allow laboratory scale directed evolution of new peptide macrocycle inhibitors. This work is expected to yield new avenues and technologies for development of peptide macrocycle-based therapeutics.