{"id":41559,"date":"2025-10-13T14:32:03","date_gmt":"2025-10-13T18:32:03","guid":{"rendered":"https:\/\/www.eng.ufl.edu\/news\/?p=41559"},"modified":"2025-12-15T11:31:59","modified_gmt":"2025-12-15T16:31:59","slug":"uf-protease-inhibitor-research-targets-better-disease-treatments","status":"publish","type":"post","link":"https:\/\/www.eng.ufl.edu\/news\/research-innovation\/uf-protease-inhibitor-research-targets-better-disease-treatments\/","title":{"rendered":"UF protease-inhibitor research targets better disease treatments"},"content":{"rendered":"\n

A University of Florida professor is developing a fast, powerful tool for blocking harmful human enzymes, a process that could result in better medicines and more precise treatments for diseases. <\/p>\n\n\n\n

Researcher Carl Denard, Ph.D., a chemical engineering assistant professor, and his team have developed High-throughput Activity Reprogramming of Proteases (HARP). This platform allows researchers to find potent, selective blockers of proteases (a kind of enzyme) linked to human diseases much faster and with fewer false positive hits.  <\/p>\n\n\n\n

Funded by the National Institutes of Health\u2019s MIRA (Maximizing Investigators’ Research Award) and National Science Foundation\u2019s CAREER award, Denard\u2019s research<\/a> was published late last month by the American Chemical Society\u2019s ACS Publications.  <\/p>\n\n\n\n

Proteases are enzymes that cleave other proteins.  <\/p>\n\n\n

\n
\"Ph.D.
Ph.D. student Samantha Martinusen serves on the UF team investigating protease inhibitors.<\/figcaption><\/figure>\n<\/div>\n\n\n

\u201cThey are involved in almost every biochemical pathway in your cells \u2014 activating other enzymes, activating proteins, degrading proteins to recycle, activating immune responses,\u201d Denard said. <\/p>\n\n\n\n

HARP is a yeast-based system that helps scientists quickly find and study strong, specific inhibitors for proteases. By pulling out nanobodies (tiny antibody-like proteins) that can shut down a target enzyme, HARP can speed the development of new drugs for viral infections, cancers or inflammatory diseases, giving clinicians quicker access to safer, more precise treatments.  <\/p>\n\n\n\n

Developing drugs that block proteases is difficult. Scientists spend much time testing different molecules that do not work.  <\/p>\n\n\n\n

With HARP, if a molecule in the yeast successfully blocks one of those proteases, the yeast shows a signal on its surface, so scientists can determine which yeast cells contain effective inhibitors. This allows scientists to screen large libraries of possible inhibitor molecules and quickly find the ones that work. <\/p>\n\n\n\n

\u201cWhat HARP has done, at least in this first iteration, is directly isolate inhibitors of proteases from a pool of binders,\u201d Denard said. <\/p>\n\n\n\n

Also leading the project is former Ph.D. candidate\/now Ph.D. graduate Samantha Martinusen. The team is using computer modeling and gene sequencing to understand exactly how these inhibitors work and why they are effective. Denard said they used UF\u2019s supercomputer, HiPerGator, for the sequence analysis.  <\/p>\n\n\n\n

\u201cProteases are important for regulating every process. But they get deregulated, which means they also are involved in disease,\u201d Denard said. \u201cThe other part of it is a lot of viruses use proteases as one of the enzymes to progress to the virus’ cycle. Example: HIV. HIV protease was one of the targets for drugs back in the day. The Pfizer drug is an inhibitor of one of the COVID proteases.\u201d <\/p>\n\n\n\n

Inhibitors are used across the board to address infections, viruses, autoimmune disease and cancer \u2014 as long as you can define a target, Denard said. <\/p>\n\n\n\n

\u201cHARP\u2019s advantage is isolating these \u2014 you get to them, you make them more efficient, Denard said. \u201cWe could, in principle, target proteases that are involving any disease as long as targeting that protease leads to a beneficial therapeutic outcome.\u201d <\/p>\n\n\n\n

And targeted therapeutics, he added, \u201cis ultimately the goal.\u201d  <\/p>\n","protected":false},"excerpt":{"rendered":"

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