Intermolecular Phosphoryl Transfer of N‐Phosphoryl Amino Acids

Abstract

AbstractN‐Phosphoryl amino acids (NPAAs) are a novel series of N‐terminal‐activated amino acids that act as the energy source and phosphoryl donor in intra‐ and intermolecular phosphoryl transfer to form “high‐energy” species, such as acetyl phosphate and aminoacyl phosphates, and in the self‐assembled synthesis of polypeptides under mild aqueous conditions. In this work, the chemical reactivity of N‐mono(methoxyphosphoryl)glycine as a representative was investigated in detail by using a combination of the stable‐isotope‐labeling (15N) technique, 31P NMR, ESI‐MS/MS and LC‐MS. The phosphoryl group of NPAAs can be transferred intermolecularly to the carboxy group of another molecule through intramolecular cyclic pentacoordinate phosphoric–amino acid anhydride intermediates. In addition to C‐terminal activation by phosphate anhydride, amino acids can also be self‐activated by N‐phosphorylation. This information not only provides some interesting clues for understanding the active role of the phosphoryl group in living systems, but also shows that the origin of life might be attributed to the chemical evolution of N‐phosphoryl amino acids.