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International scientific teams work with biologists at University of Kansas, find potential approach against parasites

Research teams from the National Institutes of Health and abroad have identified the first inhibitor of an enzyme long thought to be a potential drug target for fighting disease-causing parasites and bacteria. 

The teams, led by NIH’s National Center for Advancing Translational Sciences (NCATS) and University of Tokyo scientists, sorted through more than 1 trillion small protein fragments called cyclic peptides to uncover two that could shut down the enzyme. The finding, reported April 3, 2017 in Nature Communications, could set the stage for the potential development of new types of antimicrobial drugs.

NCATS’ expertise in early stage, pre-clinical molecule discovery helped the teams find potential drug candidates that could have implications for millions of people worldwide. 

“The work is an excellent demonstration of how NCATS delivers on its mission to provide improvements in translational processes.  Scientists have shown that a therapeutic target, previously considered undruggable by pharmaceutical companies, is actually druggable through a non-traditional therapeutic agent.”

Anton Simeonov, Ph.D., scientific director, NCATS Division of Pre-Clinical Innovation
201701403 Ipglycermide

An iPGM enzyme binds to an infection organism.

The target enzyme, cofactor-independent phosphoglycerate mutase (iPGM), is found in both parasites and bacteria. Several types of parasitic roundworms have iPGM, including Brugia malayi and Onchocerca volvulus, which infect roughly 150 million people living mostly in tropical regions. These parasites can cause devastating infectious diseases, such as river blindness. The enzyme also is found in bacteria, including Staphylococcus aureus, which can cause the hospital-borne infection MRSA (methicillin-resistant Staphylococcus aureus), and Bacillus anthracis, which causes anthrax.

Several infectious organisms are potentially susceptible to an iPGM inhibitor,” said co-corresponding author James Inglese, Ph.D., director, NCATS Assay Development and Screening Technology Laboratory. “The team dubbed the inhibitor peptides ‘ipglycermides,’ which represent a powerful class of iPGM inhibitors. In theory, such a drug could become a broad spectrum anti-parasitic and anti-bacterial treatment.”

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