A new four-base genetic helix, yDNA, composed of widened benzopyrimidine-purine pairs

Abstract

We describe the properties of stable DNA-like self-assembled helices composed entirely of base pairs involving two new size-expanded pyrimidines. We term this new helix geometry "yDNA" (an abbreviation of "wide DNA"). The new pyrimidine analogues, yT and yC, are increased in size by benzo-homologation and have a geometry that is distinct from previous size-expanded pyrimidines. The yT and yC deoxyribosides were incorporated into oligodeoxynucleotides designed to form four pairs: yT-A, A-yT, yC-G, and G-yC. Helices were characterized by thermal denaturation, mixing data, and circular dichroism spectra. Results showed that highly stable double-stranded helices were formed in several sequence contexts. The data further showed that yT and yC could be segregated onto one strand and used to bind to natural strands of DNA with high sequence selectivity. The combination of yC, yT, G, and A make up a new selective, self-assembling four-base genetic pairing system that functions in many respects like natural DNA, but which is structurally distinct. The results establish that multiple variants of size-expanded DNA-like helices are feasible and suggest the possibility of a future eight-base genetic system based on the yDNA geometry. Finally, the high binding selectivity, affinity, and fluorescence of yDNA strands may yield useful applications in detection of nucleic acid sequences.