Molecular structure of deoxycytidyl–3′– ethylphosphonate (RP) 5′–deoxyguanidine, d[Cp(CH3)G]. A neutral dinucleotide with Watson-Crick base pairing and a right handed helical twist

Abstract

The crystal structure of d[Cp(CH3)G] has been determined as part of a project to study the mechanism of the B----Z transition in DNA. The asymmetric unit contains two dinucleotides and the equivalent of 7.5 water molecules, partially disordered over 12 definable positions. The two symmetry-independent dinucleotides form a duplex with Watson-Crick base-pairing and a right-handed helical sense. Comparison with previously determined structures of the B and A conformation showed that this duplex is closer to B than to A but significantly different from B. It corresponds to a stretched out helix with a 4 A rise per base pair and a helical twist of 32 degrees. This structure may serve as a model for the bending of DNA in certain situations. The configuration at the methyl phosphonate is RP, and a mechanism, based on this assignment, is presented for the B----Z transition in DNA.

The SP Diastereomer of a Dinucleoside Methylphosphonate Methanol Solvate Containing Thymine and N3-Methyl-4-thiothymine Bases

“…The absolute configuration at the phosphorus centre in (1) is S. The atoms around this centre form a distorted tetrahedron with bond lengths and angles similar to those found in the crystal structures of the other dinucleoside methylphosphonates (Chacko et al, 1983;Han et al, 1990;Szab6 et al, 1993). The compound adopts an extended completely unstacked conformation with a distance between the two anomeric C atoms of 7.71 (2)A.…”

“…methylphosphonates) and their potential applications in the antisense strategy for the artificial control of gene expression has stimulated wide interest in this class of compounds (Englisch & Gauss, 1991;Miller, 1989). In contrast, only three solid-state structures of dinucleoside methylphosphonates are known to date, namely SpdAp(Me)T (Chacko, Lindner, Saenger & Miller, 1983), Rp-dCp(Me)G (Han et al, 1990) and SpTp(Me)sT (where sT is 4-thiothymidine) (Szab6, Norrus, Norrestam & Stawifiski, 1993).…”

Phosphates, DNA, and the Search for Nonterrean Life: A Second Generation Model for Genetic Molecules

“…In contrast, A SO 2 U crystallized to give a single stranded structure (30), with Watson-Crick interactions not dominating the structure. The two structures available for the methylphosphonate linked deoxynucleotide dimers d(G POCH 3 C) and d(A POCH 3 T) found strikingly parallel results (31,32). The first formed a duplex joined by six hydrogen bonds involving two Watson-Crick pairs.…”

2'-OMe-Uridin-3'-yl (3',5')-5'-O-(2'-OMe-Cytidine)-methanephosphonothioates - new building blocks for synthesis of chimeric oligonucleotides

“…Previously only few crystal structures of di(2'-deoxynucleoside) methanephosphonates have been solved by X-ray diffraction analysis, namely S P -dA PMe T, 8 R P -dC PMe G, 9 and S P -4-thioT PMe T with modified 4-thiothymine.…”