Abstract: There are provided compounds and methods for amidating the C-terminus of a polypeptide. The method include reacting a polypeptide which includes a C-terminal thioester or C-terminal selenoester with any one of a defined set of auxiliary molecules under conditions suitable to produce a polypeptide adduct which includes the auxiliary molecule chemically bound at the C-terminal of the polypeptide. In the subsequent step, the auxiliary molecule is removed from the C-terminal of the polypeptide adduct under conditions suitable to produce an amidated polypeptide.