Several templated ligation strategies have been developed, but specific caveats currently limit the utility of each strategy for CPS. Protein-templated ligations were the first demonstration of templated NCL, as peptides containing specific secondary structures can be brought into close proximity via their non-covalent interactions. While protein-templated ligation works well in a variety of contexts (e.g., self-replicating peptides, conformationally assisted protein ligations, and labeling of cell membrane proteins), the method is infeasible for most CPS applications, as peptides do not usually self-associate, and denaturants are typically required for peptide solubilization. Nucleic acids and peptide nucleic acids (PNAs) have also been used for templated ligations, as peptides conjugated with DNA or PNA can be brought into proximity via specific basepairing interactions. Nucleic acid-templated ligations complete quickly with only nM-pM template, but DNA/PNA linkers cannot be removed from ligated product. In addition, this method has only been used in non-denaturing buffers, predominantly with short peptide sequences (<20 residues) that do not fully represent the diversity of amino acid functional groups. Recently, several traceless templated ligation strategies have been developed. One such method uses peptides functionalized with UV-cleavable linkers attached to either PNA or DNA handles to enable templated ligation at low peptide concentrations. This method is not yet robust enough for routine CPS applications, as the linker syntheses are intricate, and the required UV irradiation and copper-catalyzed click steps may cause oxidative damage. The Bode group has also designed a traceless templated ligation using streptavidin-binding linkers, which cleave upon amide bond formation. Although this strategy is promising, complex linker synthesis is currently needed, and the methodology has not yet been demonstrated on peptides.