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Peptides altered in a Tufts lab may revolutionize drug development

Chain reaction

After decades of drug breakthroughs, the pipeline of new therapies has slowed to a trickle. Even as pharmaceutical companies funnel billions of dollars into research and development, many medicines entering the market today are simply variations on ones that already exist.

Drugs typically target disease-causing proteins and block them from causing further harm. This approach works wonders for some conditions but has failed to reverse the majority of diseases. When it comes to autoimmune diseases, many cancers, and countless other conditions, researchers have yet to find proteins they can target—or ways to block them without deadly side effects.

Scientists in the Kritzer Laboratory at Tufts University think they have a way to break the stalemate. They are working with a type of molecules called peptides that could overcome many of the scientific barriers in drug development.

Peptides are short chains of amino acids that resemble proteins. Peptides occur in nature and can also be engineered in a lab. In fact, the Tufts team can already make billions of peptides, nearly any combination of amino acids they can dream up. In terms of drug development, peptides have the potential to target almost any disease.

Tufts chemists are testing ways to modify peptide structure to boost their effects in living cells. In order to block a protein, a drug has to pass through the cells’ membranes. Peptides are relatively floppy chains, and the Kritzer Lab has found that reinforcements can help them cross that barrier. To that end, the team is using chemical tools to staple peptides into circular structures.

“We are forcing structure on floppy, unstructured peptides,” says Joshua A. Kritzer, Ph.D., assistant professor of chemistry and director of the Kritzer Laboratory. “If we can make them stable enough, we can conquer the problem of getting them through a cell membrane.”

A decade ago, peptides were a nonstarter in the pharmaceutical industry, but their untapped potential is now garnering attention. Kritzer says, “The default method of drug development has almost run its course. Peptides could give us new ways to develop drugs for a wide range of diseases.”