A new study from Dr. Benjamin Rotstein’s lab at the University of Ottawa has unveiled a new, simple method to prepare isotope-labeled versions of drugs and diagnostics for use in preclinical and clinical research.
They developed a method to exchange a single atom in amino acids—the building blocks of proteins—to replace it with its heavy isotope, using an elaborate process that requires intense laser light.
“Drug development” means that you need to figure out how much drug to put in a person. In order to do that, you have to study what happens when that drug is put in people.
Rotstein, an associate professor in the Faculty of Medicine’s Department of Biochemistry, Microbiology and Immunology.
Dr. Rotstein’s lab started out with their experiments working like a catalyst. They used vitamin B-6 to remove the carboxylic acid from amino acids, and they found it worked like a catalyst.
So he said they were going to run it in reverse, but it turned out that the mechanism was a little different than they initially expected.
The research was done in collaboration with university colleagues and chemists at Sanofi, the French pharmaceutical company.
Dr. Rotstein’s lab did the carbon-11 studies and worked with these collaborators to uncover the mechanism of the reaction.
Scientists use radioactive carbon-11 to create a map of the brain in a patient’s brain during a PET scan.
Dr. Rotstein and his team are now studying how to make the reaction produce only one “mirror image” version of amino acids so that researchers will no longer need to separate out the mirror images after the fact.
A recent study found that a substance called 11-aminoacids-glucose is a better indicator of diabetes than traditional tests.
“We’re also using these in imaging studies now to learn about metabolism and protein synthesis rates in different tissues,” says Dr.
Read from original Paper
Odey Bsharat et al, Aldehyde-catalysed carboxylate exchange in α-amino acids with isotopically labelled CO2, Nature Chemistry (2022). DOI: 10.1038/s41557-022-01074-0