Page 16 - Abacoa Community News - July '22

Page 16, Abacoa

Scripps Research from page 15 that could produce the desired structure, exactly mimicking
the structure of GB18 found naturally in Galbulimima
people for both healing and ceremony. A tea brewed from belgraveana bark.
the bark not only induces a dreamlike state but is said to “Stone was able to devise this beautiful choreography for
ease pain and fever. To probe these effects, researchers bringing together small chemicals to assemble the complex
have isolated more than 40 unique chemicals from the constellation that is GB18,” explains Shenvi. “He developed
tree bark but have struggled to reproduce the compounds a way to build this ring motif that is unprecedented.”
in the lab or study their biology. The method that Woo devised, in fact, let him control
Now, Scripps Research scientists have developed a which side of GB18 the ring could be tacked on to – an
method to synthesize one of these chemicals known as innovation with implications for creating variants of
GB18. Their approach, described online in the journal GB18 as well as for carrying out other chemical syntheses
Nature on May 12, 2022, includes a new type of reaction involving similar rings.
that could be useful in synthesizing other chemicals. It “The way we were able to efficiently assemble these
also let them produce enough GB18 to study its effects Researchers designed a series of chemical steps, progressing molecular connections could prove useful in other
on human brain cells and discover that the chemical binds through increasingly complex molecules (shown), to contexts,” says Woo.
to opioid receptors – the same molecules targeted by synthesize GB18 (center bottom). Photo by Scripps Research Once the researchers had a means to synthesize GB18,
many painkillers. While opioid painkillers activate these they produced enough of it to use in screening experiments
receptors, however, GB18 turns them off – a function that “This goes to show that Western medicine hasn’t conducted through the National Institute of Mental Health
some researchers hypothesize could be useful in treating cornered the market on new therapeutics; there are traditional Psychoactive Drug Screening Program, run by Professor
depression and anxiety. medicines out there still waiting to be studied,” says senior Bryan Roth of UNC Chapel Hill. These screens revealed
author Ryan Shenvi, Ph.D., a professor of chemistry at that GB18 bound to two different opioid receptors in the
brain. These receptors had never before been identified
Scripps Research. “Our hope is that we can turn GB18 into
Quick Guide a useful medicine.” as targets of any GB alkaloids and represent the first new
receptors linked to Galbulimima belgraveana activity in
In the 1950s, Galbulimima belgraveana caught the

To Autism attention of Australian researchers, who began isolating more than 35 years.

and studying its chemicals, called GB alkaloids. Some GB
Now, the researchers are further studying the exact
alkaloids were found to decrease smooth muscle spasm.
biological impact of GB18’s binding to the opioid receptors.
Interventions Some increased heart rate, whereas others decreased it. While opioid drugs involved in the ongoing overdose
A structural outlier, GB18, affected mouse behavior and
epidemic will activate these receptors, GB18 seems to shut
them off. Shenvi says that may make GB18 useful as an
appeared to be psychotropic. But without the ability to
recreate the compounds in the lab, it was difficult to further antidepressant or antianxiety drug, but more work is needed
By Jim Forgan, Ph.D., pursue their potential therapeutic value. to adapt it to human use.
Licensed School While some members of the Shenvi lab recently worked Shenvi and Woo are the only authors of the study
Psychologist out ways to synthesize other GB alkaloids – described in Synthesis and target annotation of GB18. A provisional
When your child Science in March 2022 – Scripps graduate student Stone patent for GB18 has been filed by both authors.
has autism, navigating Woo tackled GB18. Its structure was particularly tricky, This work was supported by funding from the National
intervention options with a chemical ring tucked in a hard-to-access pocket, like Institutes of Health (R35GM122606; S10 OD025208), the
can be confusing and a mug handle attached to the inside of a cup instead of the National Science Foundation (CHE 1856747) and the Skaggs
overwhelming when outside. Woo discovered a series of chemical steps, however, Graduate School.
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