Triggerless Bio-Orthogonal Proximity-Induced PNA Ligation Using 2,5-Dioxopentanyl (DOP) Functionality

Peptide nucleic acids (PNAs) are emerging tools in the construction of nanostructures possessing self-assembly properties similar to those of DNA but featuring enhanced stability and chemical flexibility. Templated-ligation approaches can be exploited to stabilize the formed nanoproducts, with bio-orthogonal methods preferred for compatibility with natural components. This chapter outlines design requirements and protocols for conducting triggerless bio-orthogonal PNA ligation in solution and on glass surfaces, along with an electrophoretic monitoring protocol for assessing the outcome of solution ligation.