Preformed Selenoesters Enable Rapid Native Chemical Ligation at Intractable Sites

Going pro: The first facile Pro–Cys ligation using a preformed prolyl selenoester is reported (see scheme; P=peptide). In a comparative study of peptide selenoesters in native chemical ligation peptide α-selenoesters are shown to be superior acyl donors and result in rate enhancements of at least two orders of magnitude when compared to the well-established peptide α-thioesters. This method permits rapid chemical ligation even at previously intractable sites, such as Pro-Cys.