Tryptophan as a Functional Replacement for ADP-ribose-arginine in Recombinant Proteins

Bacterial toxins such as cholera toxin and diphtheria toxin catalyze the ADP-ribosylation of important cellular target proteins in their human hosts, thereby, as in the case of cholera toxin, irreversibly activating adenylyl cyclase. In this reaction, the toxin transfers the ADP-ribose moiety of Nicotinamide Adenine Dinucleotide (NAD) to an acceptor amino acid in a protein or peptide. ADP-ribosylation leads to a peptide/protein with altered biochemical or pharmacological properties. Mammalians proteins catalyze reactions similar to the bacterial toxins. The ADP-ribosylated proteins represent useful pharmacological agents, however, their use is limited by the inherent instability of the ADP-ribose-protein linkage.

The NIH announces a new technology wherein recombinant proteins are created that substitute tryptophan for an arginine, thereby making the protein more stable, and better suited as agents for therapeutic purposes. The modification creates an effect similar to ADP-ribosylation of the arginine. An example of a protein that can be modified is the defensin molecule, which is a broad-spectrum antimicrobial that acts against infectious agents and plays an important role in the innate immune defense in vertebrates.