Finding REMO: A Sequencing Method for Recognition-Encoded Melamine Oligomers

Recognition-encoded melamine oligomers (REMO) are synthetic polymers based on an alternating triazine-piperazine backbone equipped with side chains that promote sequence-selective formation of duplexes and provide a basis for molecular replication via template-directed synthesis. Here we report the development of a method for determining the sequence of a REMO using a backbone fragmentation strategy. Methyl iodide was used to selectively methylate nitrogen atoms on the backbone without alkylating sites on the side chains. Nitrogen quaternisation generated electrophilic sites on the backbone that underwent aminolysis in methylamine solution. Each chain cleavage reaction generated three different fragments that were detectable by LCMS. This two-step fragmentation procedure was verified as a viable sequencing method for REMO of different length equipped with a variety of different side chains. The sequencing method was also used to investigate the fidelity of a replication process using base-filling with a mixed sequence REMO template.