FROM BREAKING TO MAKING COVALENT BONDS FOR NEW CHEMISTRY

Alexander Deiters

Alexander Deiters, professor of chemistry in the Kenneth P. Dietrich School of Arts and Sciences, focuses his work on creating synthetic organic molecules with new architectures and new biological functions.

His lab is well known for engineering “optical switches,” which are molecular probes used for understanding protein interactions. They start by expanding the genetic code of cells to create light-responsive amino acids. When these amino acids are incorporated into proteins, the proteins’ functions are blocked until they are exposed to light. The light breaks covalent bonds and activates the proteins.

“By engineering the genetic code from 20 to 21 amino acids, we enable fundamentally new chemistry to proteins inside that cell,” says Deiters. “This allows us to investigate the protein to find disease relevance or the discovery of new biological mechanisms in a way that has never been done before.”

More recently, his lab is transitioning from the science behind breaking covalent bonds in biological systems, to making them. Using aptamers, the research group can transfer things like fluorescent labels or drugs onto a target protein through covalent bond formation. This method shows promise for the development of new diagnostics and targeted therapeutics.

From another bond-forming project in 2023, Deiters and collaborators in the School of Medicine and Swanson School of Engineering published their groundbreaking work in Nature Communications that devised a solution to broaden the versatility of engineered CAR T-cells through covalent modification. The team engineered CAR T-cells that carry SNAPtag, a DNA repair enzyme engineered to label proteins. SNAPtag covalently bonds with benzylguanine, which is attached to an antibody. This universal approach allows the programming of CAR T-cells to recognize multiple tumor targets in a tunable fashion, which opens the door for safer and more effective CAR T treatment.

“We really try to utilize covalent bond formation to provide enhanced treatment modalities for diseases,” says Deiters. “But at the same time, we’re also looking to provide new research approaches to move the whole field forward.”