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Technique Developed to Extend Peptide Lifetimes

Transthyretin protein

Transthyretin protein structure (TFoss, Wikimedia Commons)

3 November 2015. A pharmacy lab at University of the Pacific developed a technique for extending the longevity of peptides, short amino acid chains found in many biologic drugs. The discovery from the lab of pharmacy professor Mamoun Alhamadsheh is described in this month’s issue of Nature Reviews Drug Discovery, and earlier in Nature Chemical Biology (paid subscriptions required).

Peptides are a vast potential source for engineered biologic drugs, and the building blocks of many new medications. Because of their small size and chemistry, peptides can be aimed precisely at target receptors, often with fewer side effects.

In their native state, however, peptides degrade quickly in the blood and kidneys, and are cleared from the body. As a result, to be effective peptides need to be taken frequently and in larger dosages. To increase their longevity in the body and avoid more frequent administration, peptides are sometimes combined with other compounds into macromolecules, which can interfere with binding to their target receptors, thus reducing their effects.

Alhamadsheh and colleagues in Stockton, California take a different path to extending peptide lifetimes. “In our approach,” says Alhamadsheh in a university statement, “we tagged peptides with a compound that enables it to hitch a ride on a larger protein in blood. This allows the peptides to avoid degradation and survive in the body much longer.”

The Pacific team engineered their peptides to bind with the protein transthyretin. This protein is produced mainly in the liver, and transported throughout the body carrying vitamin A and the hormone thyroxine. By binding with transthyretin, peptides are protected against degradation from enzymes in the blood, while maintaining their potency.

The researchers tested their technology in the lab with a peptide that stimulates receptors for gonadotropin-releasing hormone or GnRH, produced in the pituitary gland. Their tests show binding the peptide with transthyretin extends its lifetime, without compromising its binding ability.

In the Nature Chemical Biology article, the authors report filing for a patent on the technology.

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