Conformation of the phosphate-methylated DNA dinucleotides d(CpC) and d(TpC). Formation of a parallel miniduplex exclusively for the S configuration at phosphorus

Abstract

It has been shown that the phosphate-methylated DNA dinucleotides d(CpC) (1) and d(TpC) (2) form a parallel miniduplex exclusively for the S configuration on phosphorus, which corresponds with outward orientation of the methyl group from the helix into the solvent. The melting temperatures (T, values) of the parallel duplexes of (Sp)-l and (Sp)-2 are 33 "C and 26 "C, respectively. The phosphate-sugar backbone strands adopt a standard right-handed geometry. The imino resonances in the 600-MHz 'H NMR spectra strongly point at C C base pairing via two symmetry-related NH,--N hydrogen bonds, as was also observed in the X-ray crystal structure of 2'-deoxycytidine. From our previous work, it is known that phosphate-methylated d(TpT) forms parallel miniduplexes with an equal stability for the Sp and R p diastereoisomers. Therefore, it is concluded that the RP configuration (which is associated with location of the methyl group inside the helix groove) is unfavorable in the case of C-C base pairing. This conclusion was corroborated by AMBER molecular mechanics calculations, which showed that the larger propeller twist angle for C-C base pairing (-41"), in comparison with T-T base pairing (=25"), results in narrowing of the helix groove.

Modified RNA with a Phosphate-Methylated Backbone. A Serious Omission in Our (Retracted) Study at HIV-1 RNA Loops and Integrated DNA. Specific Properties of the (Modified) RNA and DNA Dimers

“…In an article dealing with the formation of the phosphate-methylated DNA dimers d(C P C) and d(T P C) and their ability to form parallel mini-duplexes for the S-configuration only, an unusual mode of base-base stacking was derived [21].…”

“…From the Equations (1) and (2) the values for n and ∆H can be abstracted. For r(2ꞌ-OMe)C P U with S P -configuration n = 2.04 with a relatively high ∆H value of 73 kcal/mol, although considerably smaller in comparison with the corresponding phosphate-methylated DNA, d(T P C) [1] [21]. We hypothesize, taking into account the fundamental geometric differences between the A-and B-geometry, that the spatial alignment of both type of duplexes causes the difference in ∆H focused on the intermolecular interaction in the formation of aggregates.…”

Dna Systems for B-Z Transition and Their Significance as Epigenetic Model: The Fundamental Role of the Methyl Group

“…The latter duplex is formed only with the S-chirality of phosphorus. [48] Molecular modeling studies on the duplex with thymine-thymine pairing demonstrate a remarkably slim, parallel geometry with eight residues per turn and a substantial reduction of the helix diameter in comparison with the usual antiparallel B-DNA. For the thymine-thymine base pairs, stable duplexes are formed, as was confirmed by their exceptionally high melting-transition temperatures for relatively short fragments.…”

The Chemical and Biochemical Properties of Methylphosphotriester DNA

“…[23,24] Similar observations were made for methylphosphotriester DNA showing parallel T=T O 4 -H-N 3 pairing, and C=C N 4 -H-N 3 pairing only for S P chirality. [25,26] This exclusive methylation resulted in an extended investigation of the methylphosphotriester DNA of the T hexamer, the C hexamer, and the mixed dodecamer. These oligonucleotides were prepared following a different method.…”