News Feature | January 31, 2014

ADEPS Are A New Class Of Drugs To Kill Bacteria

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By Cyndi Root

Researchers at Brown University have enhanced the potency of a new class of drugs, providing a novel way to target drug-resistant bacteria. Acyldepsipeptides (ADEPs) are molecules that may provide hope in attacking bacteria that have become resistant to antibiotics. Brown researchers in partnership with the National Science Foundation (NSF) and the National Institutes of Health (NIH) have published their findings in the Journal of the American Chemical Society.

Acyldepsipeptides

ADEPs attack bacteria in a unique way, by reconstructing the pathway where cells dispose of bad proteins. Since resistance to antibiotics is increasing, is becoming a focus of research efforts, and no other drug has the same kind of efficacy, ADEPS present a viable possibility. Jason Sello, professor of chemistry at Brown University and the lead author said, “The molecules that we have synthesized are among the most potent antibacterial agents ever reported in the literature.”

The ADEP molecule is like a cellular trash man. A protein called CLpP works in bacterial cells and destroys mutant or damaged cells that threaten the health of the bacteria. When ADEP binds to CLpP, CLpP becomes much less discriminatory, not only destroying damaged proteins, but also healthy proteins, thereby killing the bacteria. ADEP binding to CLpP is like a “cellular garbage disposal,” said Sello.

Increasing the potency of ADEPs has been a research issue, but Brown researchers have been able to increase ADEP potency by up to 1,200 times. “The work is significant because we have outlined and validated a strategy for enhancing the potency of this promising class of antibacterial drug leads,” said Sello.

ADEPs were first discovered in some bacterial strains. They exist naturally and provide defense. Sello’s group and other groups have been investigating synthetic analogues to ADEPs with the hope of inventing new drugs. Scientists have shown that ADEPs are effective in treating infection, pneumonia, and tuberculosis in the laboratory and bacterial infections in rodents.

Brown scientists will continue to work with the NSF and the NIH, proceeding to trials in mice. Researchers at MIT helped in the current study, so they and other researchers may be called on in the next stage of drug discovery. 

Sources:

http://pubs.acs.org/doi/abs/10.1021/ja410385c

http://news.brown.edu/pressreleases/2014/01/adeps