ADVERTISEMENT

Pedro García Barrantes

Medicinal chemistry mastermind is discovering new leads for treating psychiatric diseases

by Ryan Cross
August 20, 2018 | APPEARED IN VOLUME 96, ISSUE 33

Pedro García Barrantes had never heard of Vanderbilt University until he met Joshua Bruner, a graduate student in Craig Lindsley's lab at the Nashville institution. At a young chemists' conference in Brazil in 2011, "everyone else from the U.S. was complaining about their adviser except for Bruner," García Barrantes says. "That struck me."

At the time, García Barrantes was in a chemistry master's degree program in his native Costa Rica. Although he'd already earned a doctor of pharmacy, he was lured back to school to chase his dream of discovering drugs. "I realized the industry in Costa Rica was very focused on generic drugs, and I wanted to discover new molecules," he says.

When he came to my lab he could have already had a six-figure-salary job, but he wanted a career developing medicines to save lives.
Craig Lindsley, Vanderbilt University

Emboldened by his meeting with Bruner, García Barrantes applied to join Lindsley's lab. As a grad student at Vanderbilt, he began balancing multiple projects, including the first total synthesis of a rare molecule produced by a marine sponge and the discovery of compounds for psychiatric diseases.

That work swiftly brought him toward his goal of inventing new drugs. He joined a team studying mutant versions of a protein that had recently been identified in the brains of people with schizophrenia. This protein, called metabotropic glutamate receptor subtype 1 (mGlu1), is normally involved in excitatory brain-cell signaling, but the mutant versions were too quiet. García Barrantes wanted to see if turning up mGlu1 activity with allosteric activators could restore the protein's function.

After synthesizing hundreds of compounds, García Barrantes ran a series of studies during which he morphed weak activators into the best ones currently available.

Data from an upcoming publication show that his mGlu1 allosteric activators have antipsychotic effects in mouse models. Lindsley thinks the molecules could spur a new wave of psychiatric drug discovery. "When we've given seminars on these, the interest from industry is just enormous," Lindsley says.

García Barrantes moved to Boston for a brief postdoc at MIT and in February joined Vertex Pharmaceuticals, where he is working on rare disease drug discovery. "When he came to my lab he could have already had a six-figure-salary job, but he wanted a career developing medicines to save lives," Lindsley says. "I think he will become one of the most productive and insightful medicinal chemists in the field."

Watch García Barrantes speak at the American Chemical Society national meeting on Aug. 20 in Boston.
Credit: C&EN/ACS Productions

Vitals

Current affiliation: Vertex Pharmaceuticals

Age: 33

Ph.D. alma mater: Vanderbilt University

I've overcome adversity in the lab by: Learning to be resilient and coping with the unexpected challenges of research. While working on a total synthesis, in the last of many steps, the starting material decomposed. I quickly found the hard way that the original route was not going to be productive, so I decided to take everything I learned from the molecule, redesigned the route, and moved forward with another approach, and it paid off.

If I were an element, I would be: Nitrogen because of its flexibility and versatility. Nitrogen can have different oxidation states and induce different geometries and reactivities in molecules. It is also present in a vast number of bioactive molecules and can engage in very interesting interactions with drug targets.

Latest TV show binge-watched: "The Walking Dead" and spin-off "Fear the Walking Dead"

Walk-up song: "In One Ear" by Cage the Elephant

Research at a glance


Credit: Science/Protein Databank/Will Ludwig/C&EN/Shutterstock

Mice modeled to display features of schizophrenia have high levels of dopamine release from the dorsal striatum. García Barrantes designed selective allosteric activators of metabotropic glutamate receptor subtype 1 (mGlu1) that attenuate dopamine release and correct behavioral deficits in those mice.

5 /5 FREE ARTICLES LEFT THIS MONTH Remaining
Chemistry matters. Join us to get the news you need.

If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.

ENJOY UNLIMITED ACCES TO C&EN

Drug Discovery

Pedro García Barrantes

Medicinal chemistry mastermind is discovering new leads for treating psychiatric diseases

by Ryan Cross
August 19, 2018 | APPEARED IN VOLUME 96, ISSUE 33

09633-cover5-PedroGarciaBarrantes.jpg
Credit: Joel Kimmel
Pedro García Barrantes
09633-cover5-research.jpg
Credit: Science/Protein Databank/Will Ludwig/C&EN/Shutterstock

Mice modeled to display features of schizophrenia have high levels of dopamine release from the dorsal striatum. García Barrantes designed selective allosteric activators of metabotropic glutamate receptor subtype 1 (mGlu1) that attenuate dopamine release and correct behavioral deficits in those mice.

Vitals

Current affiliation: Vertex Pharmaceuticals

Age: 33

Ph.D. alma mater: Vanderbilt University

I’ve overcome adversity in the lab by: Learning to be resilient and coping with the unexpected challenges of research. While working on a total synthesis, in the last of many steps, the starting material decomposed. I quickly found the hard way that the original route was not going to be productive, so I decided to take everything I learned from the molecule, redesigned the route, and moved forward with another approach, and it paid off.

If I were an element, I would be: Nitrogen because of its flexibility and versatility. Nitrogen can have different oxidation states and induce different geometries and reactivities in molecules. It is also present in a vast number of bioactive molecules and can engage in very interesting interactions with drug targets.

Latest TV show binge-watched: “The Walking Dead” and spin-off “Fear the Walking Dead”

Walk-up song: “In One Ear” by Cage the Elephant

Three key papers

“Total Synthesis of Gombamide A” ( Org. Lett. 2016, DOI: 10.1021/acs.orglett.6b01825)

“Development of Novel, CNS Penetrant Positive Allosteric Modulators for the Metabotropic Glutamate Receptor Subtype 1 (mGlu1), Based on an N-(3-Chloro-4-(1,3-dioxoisoindolin-2-yl)phenyl)-3-methylfuran-2-carboxamide Scaffold, That Potentiate Wild Type and Mutant mGlu1 Receptors Found in Schizophrenics” (J. Med. Chem. 2015, DOI: 10.1021/acs.jmedchem.5b00727)

“Chemical Modulation of Mutant mGlu1 Receptors Derived from DeleteriousGRM1 Mutations Found in Schizophrenics” (ACS Chem. Biol. 2014, DOI: 10.1021/cb500560h)

Stories in C&EN about Pedro García Barrantes’s work

Pedro García Barrantes had never heard of Vanderbilt University until he met Joshua Bruner, a graduate student in Craig Lindsley’s lab at the Nashville institution. At a young chemists’ conference in Brazil in 2011, “everyone else from the U.S. was complaining about their adviser except for Bruner,” García Barrantes says. “That struck me.”

At the time, García Barrantes was in a chemistry master’s degree program in his native Costa Rica. Although he’d already earned a doctor of pharmacy, he was lured back to school to chase his dream of discovering drugs. “I realized the industry in Costa Rica was very focused on generic drugs, and I wanted to discover new molecules,” he says.

Emboldened by his meeting with Bruner, García Barrantes applied to join Lindsley’s lab. As a grad student at Vanderbilt, he began balancing multiple projects, including the first total synthesis of a rare molecule produced by a marine sponge and the discovery of compounds for psychiatric diseases.

That work swiftly brought him toward his goal of inventing new drugs. He joined a team studying mutant versions of a protein that had recently been identified in the brains of people with schizophrenia. This protein, called metabotropic glutamate receptor subtype 1 (mGlu1), is normally involved in excitatory brain-cell signaling, but the mutant versions were too quiet. García Barrantes wanted to see if turning up mGlu1 activity with allosteric activators could restore the protein’s function.

After synthesizing hundreds of compounds, García Barrantes ran a series of studies during which he morphed weak activators into the best ones currently available.

Data from an upcoming publication show that his mGlu1 allosteric activators have antipsychotic effects in mouse models. Lindsley thinks the molecules could spur a new wave of psychiatric drug discovery. “When we’ve given seminars on these, the interest from industry is just enormous,” Lindsley says.

García Barrantes moved to Boston for a brief postdoc at MIT and in February joined Vertex Pharmaceuticals, where he is working on rare disease drug discovery. “When he came to my lab he could have already had a six-figure-salary job, but he wanted a career developing medicines to save lives,” Lindsley says. “I think he will become one of the most productive and insightful medicinal chemists in the field.”

X

Article:

This article has been sent to the following recipient:

Leave A Comment

*Required to comment