O is for aldehyde: using pyrrolysine analogues to introduce reactive carbonyls into proteins for bioconjugation

Chemical modification of proteins is a rapidly expanding area of interest with tangible effects upon society. Numerous therapeutics consisting of chemically functionalised proteins see mainstream use in clinical settings, such as proteins enhanced with polyethylene glycol or antibodies linked to anti-cancer drugs. Such modifications are no mean feats however, requiring powerful chemistry to modify the protein with the desired tag in a selective and controlled manner whilst retaining the native protein function. Some contemporary strategies achieve this through the introduction of functionality not commonly found in nature, with a key area of interest being protein aldehydes. This work reveals new methods for the installation of such aldehydes into proteins and their suitability as handles for site-specific chemical protein modification.