Template-directed ligation of recognition-encoded melamine oligomers

Abstract

The templated ligation of DNA oligomers allows quantitative coupling reactions at very low concentrations and with very high selectivity. Recognition-encoded melamine oligomers (REMO) also form sequence-selective duplexes, and it should therefore be possible to ligate them in the same way. REMO duplex formation is based on H-bonding interactions between phosphine oxide (A) and 4-nitrophenol (D) recognition units, so two DDD oligomers could be ligated using an AAAOAAA template (where O represents a blank recognition unit). Two different types of chemistry were investigated: S_NAr coupling of a piperazine with a dichlorotriazine, and CuAAC coupling of an azide and an alkyne. Quantitative templated ligation was observed in the presence of competing reagents, whereas statistical mixtures of different products were obtained in the absence of template. The effective molarities for the intramolecular reaction between the two substrates bound to the template are 5 mM for the S_NAr coupling and 3 mM for the CuAAC coupling, which means that template-directed REMO ligations at micromolar concentrations give quantitative yields with very high selectivity in the presence of large amounts of competing reactants.