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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
Author(s) -
Sonavane Uddhavesh B.,
Sonawane Kailas D.,
Morin Annie,
Grosjean Henri,
Tewari Ravindra
Publication year - 1999
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/(sici)1097-461x(1999)75:3<223::aid-qua12>3.0.co;2-e
Subject(s) - protonation , chemistry , substituent , intramolecular force , stereochemistry , hydrogen bond , base pair , uridine , molecule , rna , dna , biochemistry , organic chemistry , ion , gene
N 6 ‐( N ‐threonylcarbonyl)adenine (tc 6 Ade), N 6 ‐methyl‐ N 6 ‐( N ‐threonylcarbonyl)adenine (m 6 tc 6 Ade), and 2‐methylthio‐ N 6 ‐( N ‐threonylcarbonyl)adenine (mS 2 tc 6 Ade) are characteristic modified bases that are found 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 6 Ade and mS 2 tc 6 Ade 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 6 Ade and mS 2 tc 6 Ade 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 6 tc 6 Ade, 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. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 75: 223–229, 1999