Improved Chemical Strategy To Offer Better Drugs for Osteoporosis, Diabetes
Researchers have built a version of a parathyroid hormone which is capable of resisting degradation in laboratory mice, according to a new study. The hormone has been developed by swapping the replacement parts into the backbone of a synthetic hormone.
Researchers said the altered hormone can stay around longer and at much higher concentration.
"Receptors have evolved to recognize a very specific signal in a sea of biological fluids that is full of molecular messages," said Sam Gellman, professor of chemistry at the UW, in the press release.
"We're excited because we have preserved the ability to activate the receptor" by altering the backbone of the hormone, which holds the essential contact points in place, Gellman said. "While retaining, even enhancing, the signaling ability, we have diminished the peptide's susceptibility to the biodegradation mechanisms that nature uses to eliminate signals over time."
Peptides are known to be the segments of proteins and peptide hormones, like the better-known steroid hormones such as estrogen and testosterone can covey a signal to billions of cells at once even at very small concentration.
"A substantial group of receptors, including some involved in diabetes, respond to peptide signals, but peptides are quickly degraded in the body. Our approach seems to suggest a general strategy to retain the ability to target a specific receptor while diminishing the action of degrading enzymes. The key is that the receptor is looking for one shape while the destructive enzyme seeks a different shape," Gellman added.
Gellman also added that the idea of replacing segments of the peptide backbone with artificial units once seemed heretical. "Most people expected that you could not change the backbone, which alters the spacing and orientation of the essential contact points, without making the molecule unrecognizable to the receptor."
The study has been published in the journal Nature Biotechnology.