A new protein structure has been developed inside a laboratory that could help more accurately target diseased targets and increase a drug’s potency. Swiss researchers at the Laboratory of Therapeutic Proteins and Peptides at Ecole Polytechnique Federale De Lausanne (EPFL) have discovered a new synthetic amino acid that can be used for a whole new line of drugs, and published their findings in the journal Nature Chemistry.

Developing new and effective drugs is a feat many research labs struggle with, and up until now, most of the amino acid-based drugs occurred naturally, such as insulin hormones, vancomycin antiobiotics, cyclosporine immunosuppressives, and other drugs. There’s a wide variety of peptides and proteins, but only 20 different natural amino acids, and they become unique 3D structures when strung together. The synthetic structure the team at EPFL created has a similar structure to cysteine, a sulfur amino acid, but is considerably more effective.

"This was unexpected,” the study’s lead author Christian Heinis, a biochemist at EPFL, said in a press release. "Usually when you tamper with a natural molecule, you end up making it worse. In this case, we found the exact opposite, which is very exciting."

Diseases are increasingly emerging and overwhelming the scientific community and drug effectiveness needs to be increased in order to stop the ongoing resistance. Bacterial resistance, for example, has spread to global proportions and research has been pushed in the direction of new and innovative antibiotic development, which is just what Heinis’ research team has delivered. By mimicking naturally occurring chemical structures, the field can move forward with new and improved peptide and protein tools for fighting ever-evolving diseases.

Cysteine is able to form a bridge to the cysteine amino acid next to it, which is how it forms a 3D structure; however, the newly synthesized amino acid is able to form two bridges when it connects to another cysteine-like amino acid. Laboratory tests found the newly synthesized amino acid is eight times more effective and fights disease at a 40 times higher rate than the naturally occurring amino acid cysteine.

When amino acids attach to one another they form 3D peptides and proteins as building blocks within the body. Heinis’ team specializes in developing double-bridged peptides known as “bicyclic” peptides and is able to target and fight disease with less troops than naturally occurring large antibodies. "In our work with bicyclic peptides, we learned that wide structural diversity in peptide libraries is key for achieving good binding,” Heinis said. “With this new amino acid, it is possible to produce highly diverse peptide structures.”

Source: Chen S, Gopalakrishnan R, Schaer T, Marger F, Hovius R, and Bertrand D, et al. Di-thiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides. Nature Chemistry 31 August 2014.