Abhishek Chatterjee’s Faculty Page
Eranthie Weerapana’s Faculty Page
Abhishek Chatterjee’s Faculty Page
Eranthie Weerapana’s Faculty Page
Researchers at Boston College used a slight rate of electrical energy to modify proteins exactly, a new and affordable tool that can be used to expand new tools for biotherapeutics and protein-based studies.
Led by chemistry professors Abhishek Chatterjee and Eranthie Weerapana, the team evolved and optimized a new electrochemical protein labeling reaction called “eCLIC,” which allows for the exact modification of site-embedded 5-hydroxytryptophan (5HTP) residues in many other proteins, adding complete proteins. . therapeutic antibodies.
The team’s good fortune marked the first time electrocatalysis was used to modify proteins in a site-specific way, they reported in a paper published in the journal Nature Chemistry, “Electrochemical labeling of hydroxyindoles with chemoselectivity for site-specific protein bioconjugation. “
Proteins are giant molecules, usually made up of a large number of amino acid monomers, Chatterjee said. The ability to selectively modify proteins at predefined sites is vital for many applications. For example, by covalently binding poisonous drugs to antibodies, it has been conceivable to deliver them to cancer cells, obtaining better curative efficacy and eliminating off-target toxicity.
Many research programs also require the connection of biophysical probes to proteins. The ability to define the site of protein modification is critical to ensuring that the proteins’ vital functions are not damaged, Chatterjee said.
“The challenge comes from the fact that all proteins are made up of 20 amino acids in combinations,” he said. “Identifying a modifiable feature at the desired site, which is not repeated elsewhere, is often tricky, making it difficult to achieve site specificity. “in protein modification. “
To overcome those challenges, the team sought to expand an approach to incorporate a non-natural amino acid into any selected site of a protein. The team completed this by revamping the cells’ translation formula to adapt it to the new amino acid 5HTP.
In addition, the researchers tried to engineer chemical reactions that could be used to selectively modify this non-plant amino acid in the presence of all plant amino acids, Chatterjee said.
“If we could do this, we could offer a general approach to generating proteins with an integrated ‘binding control’ at a predefined site. In particular, we were looking to expand a reaction that would use electrical energy to catalyze the protein modification. Chemical catalysis, as the former is economical, environmentally friendly and gentle on sensitive proteins.
Chatterjee said the team was able to overcome a challenge when they first tried to design the reaction. Typically, researchers start with small molecules, in this case 5HTP and aniline, and then move on to giant proteins.
But early attempts to react between 5HTP and anilines at the small molecule point were tricky, as 5HTP molecules preferentially reacted with each other. However, when 5HTP was incorporated into a giant protein, it could no longer react with other bound proteins. 5HTP, but reacted cleanly with an aniline, the team reported.
“If we had stuck to the classic progression, from small to large, we would have never followed eCLIC, thinking it’s too complicated,” Chatterjee said. “Instead, we evolved our reaction in a non-classical way, directly into a protein, which helped us realize how empty and selective it is in this context. “
To further advance the eCLIC plan of large-scale modification of vital protein targets, this generation has been approved by BrickBio Inc. , co-founded by Chatterjee. Future studies will focus on the progression of site-specific biotherapeutics and studies.
In addition to Chatterjee and Weerapana, the paper’s co-authors were postdoctoral researchers Soumya Jyoti, Atanu Mondal and Singha Roy; and graduate scholars Conor Loynd, Vincent J. Ovalle, Sarah E. Canarelli, Delilah Jewel and Elise D. Ficaretta.