Berkeley Lab discovery could redefine drug delivery

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Chemists at the Lawrence Berkeley National Laboratory have invented a new technique to link chemicals to proteins that could potentially change how ailments are treated.

Bioconjugation has been compared to hitching cargo onto a truck: Once the hitch, made up of amino acids, is on the truck, which represents a protein, it can transport different “cargo” throughout the body for a variety of purposes. The amino acids attached to the proteins can then function as “chemical tracking devices” or drug delivery systems.

The development of this new form of bioconjugation is noteworthy because of the novel use of an amino acid called methionine, according to study principal investigator Christopher Chang.

The amino acid cysteine has traditionally been used as an attachment to proteins in bioconjugation, but can disrupt the protein’s function. Cysteine was used primarily for its ease, rather than its precision, according to Chang.

To circumvent the unpredictability of cysteine, researchers looked to the only other available amino acid that contains sulfur –– an anchor in acid-based reactions. Now, the lab has accomplished the first example of methionine-based bioconjugation.

Methionine is a more versatile and controllable chemical hitch because it is a natural amino acid. The use of methionine also sets biocatalysis — a means of expediting chemical reactions that only takes place with natural substances — into effect.

Methionine, however, is more difficult to use because it has a carbon atom attached to its sulfur atom — blocking most hitches. The technique that resolved this dilemma has been coined redox activated chemical tagging, or ReACT. This technique links a chemical group to a protein’s sulfur atom without affecting the carbon group next to it.

The use of methionine as the protein’s “chemical hitch” both mitigates environmental concerns and allows scientists better control over where they attach the amino acid. Because of these new qualities, Chang’s discovery can be used for everything from biopharmaceuticals to energy science and water purification.

“(It’s) a chemical swiss army knife,” Chang said. “Through this one type of reaction you can use many tools.”

Chang, whose namesake lab made the discovery, has been working on the project along with a small team at Berkeley Lab since 2004 and began to make significant breakthroughs about five years ago.

While the implications of the newly published research are still not fully known, companies interested in licensing the technology have already begun to reach out, Chang said. The lab has filed patents and is currently weighing its options as well as contemplating the possibility of creating a startup.

Contact Audrey McNamara at [email protected] and follow her on Twitter at @McNamaraAud.