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School of Science awarded over $5.5M to address chemistry challenges in drug development

For Immediate Release Aug 31, 2023

INDIANAPOLIS — Three faculty members at the School of Science at IUPUI — Yongming Deng, Sébastien Laulhé and Ian Webb — will receive grants totaling $5.4 million over the next five years from the National Institutes of Health.

The awards are a part of the NIH’s National Institute of General Medical Science’s Maximizing Investigators’ Research Award, or MIRA, program. The awards are designed to provide researchers with greater stability and flexibility to enhance scientific productivity and the chances of important breakthroughs.

All three individual awards are united in their focus on potentially addressing challenges in human health through chemistry. The funded projects include studying proteins currently regarded as potential drug targets in the treatment of neurodegenerative disease; creating new chemical catalysts for use in drug development that are more sustainable and affordable than those currently in use; and expanding the medical applications of molecules currently found in anti-cancer and psychoactive drugs.

“I’m pleased to see the potentially life-changing research of Ian, Yongming and Sébastien — and our Department of Chemistry and Chemical Biology — recognized through the support of the NIH,” said John F. DiTusa, dean of the School of Science. “These awards follow a record-breaking year of funding at the School of Science in 2023 and present a tremendous start to our 2024 campaign.”

Understanding ‘disordered’ proteins to treat disease

Ian Webb Ian Webb. Photo courtesy of the School of Science

A $1.96 million grant will support the research of Ian Webb, an assistant professor of chemistry, to determine how changes in the sequence of genes, or modifications of proteins after gene expression, cause changes in protein 3D structure, which relates directly to their proper function.

Specifically, Webb and his graduate students will observe a proteins that lack a fixed or ordered three-dimensional structure, which are known as intrinsically disordered proteins, or IDPs.

Misfolded versions of IDPs are commonly found in patients of protein-misfolding diseases such as Alzheimer’s, Parkinson’s, Type 2 diabetes and ALS, making the understanding of these proteins vital to finding advanced treatments.

“Our current understanding is limited to ensemble averages of IDPs’ cellular states; most often, this is limited to studies inside the test tube,” Webb said. “Our approach will allow studies where we can simultaneously analyze the entire mixture of various mutation and modified states, which will be a huge advance for the field.”

Seeking more sustainable pharmaceutical catalysts

Sébastien Laulhé Sébastien Laulhé. Photo by Liz Kaye, Indiana University

Sébastien Laulhé, assistant professor of chemistry, will receive $1.77 million to develop sustainable strategies to generate molecules of interest to human health and human development, particularly as it relates to pharmaceuticals. He and his team of graduate and undergraduate students will focus on metal-free techniques that enable the formation of carbon-to-carbon bonds, which are the backbone of pharmaceuticals and agrochemicals.

“In particular, we will look into accessing challenging unnatural amino acids, which have been shown to have favorable bioactivities,” Laulhé said. “Our group uses blue LED lights as a replacement for metal catalysts to generate these structures. Thereby, we minimize toxic metal waste, as well as reduce the environmental footprint of manufacturing these potentially life-saving molecules.”

Using this “light-based” approach, as opposed to metal catalysts, has become increasingly popular within organic chemistry in the past decade, Laulhé added. He said these methods have the potential to make lifesaving medications more attainable, improving the lives of patients across the globe.

Advancing medical use of N-oxide catalysts

Yongming Deng Yongming Deng. Photo courtesy of the School of Science

Yongming Deng, assistant professor of chemistry, in collaboration with Jingzhi Pu, associate professor of chemistry, will receive $1.85 million to research expanding the potential medical applications of N-oxides, also known as amine oxides. These molecules are commonly used in medication, as well as anti-cancer and psychoactive drugs.

The goal of this project is to provide a greater understanding of the single-electron transfer chemistry of aromatic N-oxides, as well as its use for synthetic methodology and catalysis development. This work could expedite the design, development and manufacture of medicines to manage and treat diseases.

“This work will significantly impact human health and medicine by establishing new and practical synthetic protocols and an innovative modular catalyst system for selective carbon-hydrogen functionalization of organic molecules,” Deng said. “This will contribute to the design and development of new clinical agents.”

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