Sequence-Dependent Folding of Recognition-Encoded Melamine Oligomers

Recognition-encoded melamine oligomers (REMO) equipped with complementary 4-nitrophenol (D) and phosphine oxide (A) side chains show sequence-dependent folding properties that resemble the folding of single-stranded nucleic acids. Automated solid phase synthesis was used to obtain a series of REMO with an A at one end of the chain and a D at the other. The two complementary recognition units were separated by 0-8 blanks (O, triazines equipped with alkyl side chains). UV-vis absorption denaturation experiments with perfluoro-tert-butanol in dichloromethane solution were used to quantify intramolecular 4-nitrophenol·phosphine oxide base-pairing in these oligomers. 1,2-Folding was not detected, but the other oligomers populate 50-90% of the folded state depending on sequence. Another series of oligomers with two complementary recognition units at each end of the chain was used to investigate folding of hairpin loop and helical structures. In these systems, the folded single strand makes two base-pairing interactions, so folding is governed by the effective molarities for the two intramolecular H-bonds, EM_f, and a cooperativity parameter, α. At least four looped-out bases are required to form a stable hairpin: two hairpin sequences, ADO₄AD and ADO₅AD, showed strong positive allosteric cooperativity (α > 10) with 96% population of the folded state. The helical sequence, DAO₄AD, which showed strong positive cooperativity is consistent with a hexagonal grid model for the conformation of the backbone. These sequence-structure relationships show that favorable folding motifs arise when the positions of complementary recognition sites align with the conformational preferences of the triazine-piperazine backbone.