New medicinal chemistry and pharmacognosy faculty member to develop highly specific prodrugs to reduce the toxicity of chemotherapeutics

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January 11, 2023

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Jonathan H. Boyce, PhD, joined The Ohio State University College of Pharmacy (COP) as an assistant professor in the Division of Medicinal Chemistry and Pharmacognosy this January.

Dr. Boyce's lab will focus on developing protease-activated peptide prodrugs for cancer, which will contain specialized peptide linkers attached to chemotherapeutics resulting in reduced toxicity. Because peptides often have low cell permeability, peptide linkers will reduce drug toxicity by preventing the chemotherapeutics from entering cells.

However, once the peptide-drug conjugate reaches the tumor microenvironment, the peptide linker will be cleaved by cancer-specific proteases. The linker will be carefully designed to ensure dominant linker cleavage in the tumor microenvironment while maintaining stability in the presence of diverse healthy cells and serum.

Once the chemotherapeutic is released by proteases in the tumor microenvironment, the toxic drug would then kill tumor cells in the localized environment. This targeted approach has the potential to dramatically improve the quality of life for chemotherapy patients.

“A lot of times with chemotherapeutics, there are secondary complications that patients experience because the drugs are killing healthy cells,” Dr. Boyce said. “The linkers will help to make chemotherapy more tolerable for patients.”

It is Dr. Boyce’s desire to improve human health. His pursuit of translational research was inspired by his experiences as a postdoc at UCSF. Before joining COP, Dr. Boyce was a postdoctoral Fellow at the University of California at San Francisco (UCSF) where he developed highly selective prodrugs for infectious diseases. Dr. Boyce’s experience at UCSF gave him the foundation to create prodrugs for chemotherapy.

The influence of Dr. Boyce’s training from his PhD and postdoc is apparent. In his PhD, he learned how to make molecules. In his postdoc, he learned how to design molecules for therapeutic benefit. Below, Dr. Boyce describes how these specific experiences will enable him to tackle problems in chemotherapy.

  1. PhD Project: Synthesis of polycyclic polyprenylated acylphloroglucinol (PPAP) natural products and related analogs.

“The training in my PhD gave me the ability to make molecules efficiently, which will be essential to create chemotherapeutic prodrugs and probes. Being able to synthesize compounds rapidly is an essential component for any drug discovery program,” Dr. Boyce said.

  1. Postdoc Project: Development of antibiotic prodrugs that enable controlled release of antibiotics inside gram-negative bacteria.

“UCSF provided an optimal training ground for my transition from mainstream synthetic chemistry into translational research. Working in the labs of three professors Ian Seiple, Bill DeGrado, and Charly Craik enabled me to draw from the diverse expertise of all three mentors to tackle high-impact interdisciplinary projects that would improve human health," Dr. Boyce said.