A Divergent Strategy for Attaching Polypyridyl Ligands to Peptides

A divergent method for incorporating polypyridyl ligands into peptides is reported. Three N-Fmoc unnatural amino acids (1−3) that contain varying linkers between the α-carbon and a 2-(hydroxymethyl)pyridyl group were synthesized in enantioenriched form. These amino acids were used as anchors for incorporating multidentate ligands onto a peptide chain in a site-specific fashion. Multiple peptide−ligand conjugates were synthesized from single precursors by solution- or solid-phase methods. Peptides containing more than one metal-binding unit can be produced by this method.