Synthesizing a deadly mushroom toxin

April 11, 2018

The death-cap mushroom has a long history as a tool of murder and suicide, going back to ancient Roman times. The fungus, Amanita phalloides, produces one of the world's deadliest toxins: α-amanitin. While it may seem ill-advised, researchers are eager to synthesize the toxin because studies have shown that it could help fight cancer. Scientists now report in the Journal of the American Chemical Society how they overcame obstacles to synthesize the death-cap killer compound.

α-Amanitin achieves its impressive deadliness by acting as a potent inhibitor of RNA polymerase II, the enzyme primarily responsible for transcribing genes into the messenger molecule RNA. Using α-amanitin bound to antibodies against tumor molecules, cancer researchers have reportedly cured mice of pancreatic cancer. These conjugates are currently in human trials; however, the only way to obtain α-amanitin so far has been to harvest mushrooms, which is time-consuming and results in relatively small amounts of the compound. Synthetic production approaches have been hampered by α-amanitin's unusual bicyclic structure, among other tricky features. David M. Perrin and colleagues decided to take on the challenge to produce the toxin in the laboratory, once and for all.

The researchers had to work through three key obstacles to produce α-amanitin in the laboratory: production of the "oxidatively delicate" 6-hydroxy-tryptathionine, the an enantio- selective synthesis of (2S,3R,4R)-4,5-dihydroxy-isoleucine and a diastereoselective sulfoxidation to favor the (R)-sulfoxide. Due to its toxic nature, the researchers limited production to less than a milligram, but based on their results, they are confident that good yields are can be readily obtained by scaling up the process. The researchers also say that the development of this synthetic route will enable chemists to attenuate the toxicity and potentially improve α-amanitin's activity against cancer, something that is only made possible by the use of synthetic derivatives.
-end-
The authors acknowledge funding from the Natural Sciences and Engineering Research Council of Canada, the Canadian Institutes of Health Research and the Canadian Cancer Society.

The abstract that accompanies this study is available here.

The American Chemical Society, the world's largest scientific society, is a not-for-profit organization chartered by the U.S. Congress. ACS is a global leader in providing access to chemistry-related information and research through its multiple databases, peer-reviewed journals and scientific conferences. ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies. Its main offices are in Washington, D.C., and Columbus, Ohio.

To automatically receive news releases from the American Chemical Society, contact newsroom@acs.org.

Follow us on Twitter | Facebook

American Chemical Society

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.