Problem: The market for protein-based drugs, such as insulin and human growth hormone, has doubled over the last five years, to more than $50 billion. But making therapeutic proteins is difficult. Unlike small-molecule drugs, such as aspirin, which can be synthesized chemically, proteins are typically made by genetically engineering bacteria, growing them, and extracting the final protein from them.
It would be simpler if synthetic chemists could make small protein snippets called peptides from their amino-acid building blocks and then stitch them into complex proteins. But the process for making peptides is inefficient for chains more than 15 amino acids long. (Most therapeutic proteins contain anywhere from two to 30 times that many amino acids.) And existing techniques for joining peptide fragments are impractical.
Solution: Organic chemist Jeffrey Bode has come up with a more versatile way to connect peptides. Bode’s group discovered that two chemical groups not normally involved in peptide synthesis react to form amide bonds, the key link between amino acids. The researchers synthesized peptides using the standard chemical recipe; they then attached one of their chemical groups to either end of each peptide. Placed in water, the peptides join together. The only byproduct is carbon dioxide.
Using Bode’s scheme, researchers can in theory click any two peptides together. That might eventually let drugmakers synthesize any protein from scratch. The result could be a surge in new proteinbased therapeutics, many of which would contain chemical groups that are hard for bacteria to manufacture, but which would increase the drugs’ stability and reduce their toxicity in the body.