A mild N-alkylation method has been developed for the synthesis of N-alkylated pyridiniumcarboxylic acids, using Ag2O-H2O catalysis to enhance the low-reactivity of pyridinecarboxylic acids. Two approaches were undertaken for the synthesis of a series of GnRH antagonists containing pyridinium moieties at the side chain: (1) incorporation of Npy-alkylated D-pyridylalanine during solid phase peptide chain assembly, and (2) coupling of the N-alkylated pyridinium-carboxylic acid to the resin-bound ε-amino group of a D-lysine on a solid support.