Mini-Protein Flips May Boost Disease Treatments

Researchers find chemically modified peptides could enhance tuberculosis drug effectiveness

Published on Feb. 11, 2026

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Researchers from Penn State and the University of Minnesota Medical School have found that chemically modifying naturally occurring peptides, which are building blocks of proteins, can create more stable and effective antimicrobial agents to potentially help treat tuberculosis. The team discovered that inverting the structure of these peptides not only made them more resistant to degradation, but also dramatically increased their potency against the tuberculosis pathogen while reducing toxicity to human cells.

Why it matters

Antibiotic resistance is a growing global health concern, with many common bacterial infections becoming increasingly difficult to treat. This research explores an alternative approach to traditional antibiotics by leveraging naturally occurring peptides that could be chemically modified to create new antimicrobial agents that are less susceptible to resistance development.

The details

The researchers started with host-defense peptides (HDPs), short chains of amino acids produced naturally in the body that have shown potential for treating antibiotic-resistant infections. However, these HDPs are often unstable and quickly degraded. To address this, the team applied chemical techniques like "backbone-inversion" and "chirality switching" to make the peptides more resilient to enzymes. They found that the retro-inverted variant was not only more stable, but dramatically more potent against the tuberculosis pathogen and less toxic to human cells compared to the original molecule. Analysis showed the new shape made it more energetically efficient for the modified HDPs to penetrate and degrade bacterial cell membranes, rather than disrupting specific protein targets.

  • The research was published in February 2026 in the journal Nature Communications.

The players

Scott Medina

Korb Early Career Associate Professor of Biomedical Engineering at Penn State and corresponding author on the paper.

Sabiha Sultana

A graduate student in the Department of Biomedical Engineering at Penn State.

Diptomit Biswas

A graduate student in the Huck's Molecular, Cellular, and Integrative Biosciences program at Penn State.

Neela Yennawar

Research Professor and director of the Huck's Biomolecular Interactions Core Facility at Penn State, which assisted the project with biophysical characterization.

Hugh Glossop

Formerly a postdoctoral researcher in Medina's lab, now a fellow at the Dana-Farber Cancer Institute.

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What they’re saying

“There's a desire to create new drugs that can kill bacteria through mechanisms that are not used by traditional antibiotics. Particularly, there is an interest in molecules that may be difficult for bacteria to evolve resistance towards, providing a longer span of time for these treatments to be clinically useful.”

— Scott Medina, Korb Early Career Associate Professor of Biomedical Engineering at Penn State (Mirage News)

“When we compared the original molecule - which doesn't have any chemical modifications - to the one that we did modify, not only was the modified one more stable, but now it was also much more active. That's something that we didn't expect to see.”

— Scott Medina, Korb Early Career Associate Professor of Biomedical Engineering at Penn State (Mirage News)

What’s next

The researchers say there is more work to be done, but they envision the modified peptides could potentially be used to enhance the effectiveness of current tuberculosis drug treatments, rather than replace them entirely.

The takeaway

This research demonstrates the potential of chemically modifying naturally occurring peptides to create new antimicrobial agents that are more stable, potent, and less prone to resistance development compared to traditional antibiotics - a promising approach for tackling the growing global challenge of antibiotic resistance.