Chiral phosphorothioate analogues of B-DNA

Cruse, W. B. T.; Salisbury, Stephen A.; Brown, Tom; Cosstick, Richard; Eckstein, Fritz; Kennard, Olga

doi:10.1016/0022-2836(86)90035-5

Cited by 130 publications

(59 citation statements)

References 32 publications

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“…The compound adopts an extended completely unstacked conformation with a distance between the two anomeric C atoms of 7.71 (2)A. The torsion angles that characterize the overall geometry of (1) are given in Table 3 (1) are in the typical range for a nucleic acid fragment (Saenger, 1984), while angles a, e and y deviate substantially from the standard values and are closer to those found in some nucleic acid analogues with an extended phosphate-backbone conformation (Cruse et al, 1986;Dickerson, Kopka & Drew, 1982). Except for the methanol solvent molecule, the patterns of intermolecular hydrogen bonding between the methylphosphonate molecules in the crystal structures of (1) and Sp-Tp(Me)sT (Szab6 et al, 1993) are similar (cf.…”

Section: Commentsupporting

confidence: 54%

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

Szabó¹,

Stawiński

Carlson

et al. 1995

Acta Crystallogr C

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The structure of the non-self-complementary di-, Tp(Me)msT, C22H31NaOio-PS.CH40, has been determined and its absolute configuration at the phosphorus centre shown to be S. The 2'-deoxyribose rings of the thymidine and N 3-methyl-4-thiothymidine moieties adopt 3 T2 (C3'-exo/ C2'-endo) and 2T 3 (C2"-endo/CY-exo) conformations, respectively. Both heterocyclic bases are oriented anti relative to the sugar rings. The deoxyribose-phosphonate backbone has an extended conformation with the bases completely unstacked and tilted away from being parallel by 16 (1)°.

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Section: Commentsupporting

confidence: 54%

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

Szabó¹,

Stawiński

Carlson

et al. 1995

Acta Crystallogr C

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“…A multiple phosphorothioated analogue of [d(GC)312 crystallized in the B-type conformation with no obvious structural perturbations resulting from the switch of several oxygens to sulfurs (30). In the complex of 11-deoxydaunomycin with a phosphorothioated analogue of d(CGTACG) (24), the conformation of the DNA is similar to that in related but nonphosphorothioated DNA-anthracycline complexes (26,29).…”

Section: Discussionmentioning

confidence: 95%

Structure of nogalamycin bound to a DNA hexamer.

Williams

Egli

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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The anthracycline antibiotic nogalamycin, which binds to DNA, is composed of a planar aglycone substituted on each end to form an unusual dumbbell-shaped molecule. At one end nogalamycin contains an uncharged nogalose sugar and a methyl ester. At the other end nogalamycin contains a positively charged bicyclo amino sugar. We report the crystal structure of nogalamycin bound to the self-complementary DNA hexamer d(mSCGTsAm5CG). In this complex, the cytosines are methylated at the 5 position and the DNA contains a phosphorothioate linkage at the TpA step. Two nogalamycin molecules bind to the 6-base-pair fragment of double-helical DNA. The drug has threaded between the phosphodiester backbones with three aromatic rings intercalated within the DNA. In the major groove, the bicyclo amino sugar forms two direct hydrogen bonds to span a COG base pair and interacts indirectly with the next base pair of the duplex via a water-mediated hydrogen bond. In the minor groove, a carbonyl oxygen of nogalamycin forms a hydrogen bond directly to N2 of a guanine. The DNA base pairs are severely buckled by up to 26°and are also distorted in directions perpendicular to the Watson-Crick hydrogen bonds. This complex illustrates the deformable nature of DNA.

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“…This is hard to establish unequivocally. Only one crystal structure, for all R p -GsCGsCGsC, of an oligonucleotide phosphorothioate is known (28). Comparison with (GC) n runs of other sequences indicates that the phosphorothioates cause no structural perturbations in this instance.…”

Section: Figmentioning

confidence: 99%

“…Importantly Mg 2ϩ , an essential cofactor for the EcoRV endonuclease, strongly favors co-ordination to oxygen atoms in phosphorothioates (26 -27). Despite these differences, the single known structure of a phosphorothioate-containing oligonucleotide shows minimal structural perturbations as compared to the all-phosphate parent (28). Oligonucleotide phosphorothioates have been used to determine the stereochemical course of the reactions catalyzed by EcoRI (29) and EcoRV (30) and to probe details of protein-DNA interactions (31)(32)(33)(34).…”

mentioning

confidence: 99%