N(7)-Protonation Induced Conformational Flipping in Hypermodified Nucleic Acid Bases N~6-(N-threonylcarbonyl) adenine and Its 2-Methylthio- or N(6)-methyl- Derivatives

摘要

N~6-(N-threonylcarbonyl)adenine(tc~6Ade), N~6-methyl-N~6-(N-threonylcarbonyl)adenine(m~6tc~6Ade), and 2-methylthio-N~6-(N-threonylcarbonyl)adenine (mS~2tc~6Ade) are characteristic modified bases that are fond 3'-adjacent to anticodon in a large number of tRNAs from various organisms. The effect of protonation at the N(7) site of adenine on the preferred substituent orientations in modified bases tc~6Ade and mS~2tc~6Ade has been investigated employing the quantum chemical perturbative configuration interaction with localized orbitals (PCILO) method. Results indicate that N(7) protonation induces reorientation of the N~6-substituent, so as to allow stabilization through an intramolecular hydrogen bond involving N(7)H and the carbonyl oxygen in the ureido HN-CO-NH linkage of the N~6-substituents. The theoretically preferred "proximal" conformation of N(7)-protonated tc~6Ade and mS~2tc~6Ade enables the participation of N(6)H and N(1) sites in the Watson-Crick base pairing with uridine, just as for unmodified adenine. This may allow extended base pairing of the anticodon on the 3'-side with four bases of mRNA, permitting an altered selection of the codon triplet. However, another derivative, m~6tc~6Ade, because of the methyl group replacing the N(6) hydrogen, cannot base pair with uridine and should maintain the reading frame irrespective of the N(7) protonation status.