Pyrrolysine Analogs for Translational Incorporation into Proteins

The discovery that pyrrolysine is translationally incorporated into methylamine methyltransferases from certain methanogens in response to an in‐frame amber codon prompted detailed studies of the biochemical machinery associated with its genetic encoding. Over the past few years, significant progress has also been made in identifying a set of structural and electronic features that enable a compound to act as an effective pyrrolysine mimic. With such empirical knowledge in hand, it is becoming increasingly feasible to rationally design and synthesize new analogs with useful chemical, physical, or biochemical properties and then site‐specifically incorporate them into proteins. The present microreview highlights recent key developments in this rapidly expanding area of research.