A parallel right-handed duplex of the hexamer d(TpTpTpTpTpT) with phosphate triester linkages

Koole, Leo Lh; Genderen, van Mhp Marcel; Buck, HM Henk

doi:10.1021/ja00247a015

Cited by 45 publications

(22 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A parallel right-handed phosphate-methylated hexamer d(T P T P T P T P T P T) in solution has been experimentally established by Koole et al, and supported by molecular mechanics calculations [36]. We expect similar observations for d(C P C) in the crystalline state based on the parallel duplex formation of the corresponding phosphate-methylated S P d(C P C).…”

Section: Bio-physical Characteristics Of Phosphate-methylated Dna Cosupporting

confidence: 72%

See 1 more Smart Citation

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

Buck¹

2016

JBPC

View full text Add to dashboard Cite

After the recent publication in the Journal of Biophysical Chemistry entitled "Retracted HIV Study Provides New Information about the Status of the in Vitro Inhibition of DNA Replication by Backbone Methylation", it is of importance to review the results of Buck's group on the synthesis and conformation analyses of phosphate-methylated RNAs in order to afford information on the absence of a further investigation with regard to this de facto acceptable approach. In fact these compounds belong to the very first group of RNAs with a modified neutral backbone by phosphatemethylation. In contrast to the corresponding phosphate-methylated DNAs with a frozen Bconformation, the phosphate-methylated RNAs show an A-conformation. The latter is a prerequisite for duplex formation with (complementary) (natural) RNA. A number of experiments support this fundamental statement. After the HIV study was retracted, the overall results concerning the phosphate-methylated RNAs were published without mentioning Buck's initial proof of concept and his contributions. Generally, the (modified) dimer RNAs and DNAs possess a number of specific biophysical properties. A novel explanation is given for conflicting structural determinations.

show abstract

Section: Bio-physical Characteristics Of Phosphate-methylated Dna Cosupporting

confidence: 72%

“…This was demonstrated with a fiber diffraction pattern of d(T P T) [35] [36]. A double helical structure was established with about seven units per turn and a rise per base-pair of 3.8Å.…”

Section: Bio-physical Characteristics Of Phosphate-methylated Dna Comentioning

confidence: 80%

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

Buck¹

2016

JBPC

View full text Add to dashboard Cite

show abstract

“…The presence of DNA duplexes was ascertained independently by 'H and 31P NMR measurements on the dTlo/LysI8 complex. For thymine bases in single strands, the chemical shift of the imino protons is around 11 ppm in aqueous solution (Haasnoot et al, 1979), whereas for phosphate-methylated parallel duplexes with T-T base pairs, where the imino protons are involved in hydrogen bonding, chemical shifts of 13.4 ppm have been observed (Koole et al, 1987). At 10 "C, Le., below the T, value of 21 "C, the imino chemical shift in the dTlo/LysI8 complex is found at 13.0 ppm, which clearly indicates the formation of T-T base pairs.…”

Section: Resultsmentioning

confidence: 99%

“…Also, the duplexes between oligodeoxynucleotides with a-oriented bases and natural DNA are found to be parallel (Morvan et al, 1987;Thuong et al, 1987). Spontaneous formation of parallel duplexes has been found for phosphate-methylated pyrimidine oligomers (Koole et al, 1986(Koole et al, , 1987Quaedflieg et a!., 1990a). Methylation of the phosphate groups leads to slim, right-handed duplexes with pyrimidine-pyrimidine base pairs, due to the elimination of interstrand phosphate-phosphate charge repulsions.…”

mentioning

confidence: 99%

Peptide-induced parallel DNA duplexes for oligopyrimidines. Stereospecificity in complexation for oligo(L-lysine) and oligo(L-ornithine)

Genderen¹,

Hilbers²,

Koole³

et al. 1990

Biochemistry

Self Cite

View full text Add to dashboard Cite

It is shown that the cationic oligopeptides octadeca(L-lysine) (Lyslg) and octadeca(L-ornithine) (Orn18) can induce a parallel duplex for the natural DNA oligomer dT10 with thymine-thymine base pairs. Complexation of the ammonium groups in the peptide side chains with the DNA phosphates leads to diminished electrostatic phosphate-phosphate repulsions, which allows this T-T base pair formation. From combined NOESY NMR and molecular mechanics studies, it follows that the parallel duplex is right-handed, with the peptide located in the groove of the duplex. For the natural DNA oligomers dC10, d(C6T6), and d(T6C2T2), only Lyslg is able to induce the formation of parallel duplexes with C-C and T-T base pairs. It is shown that, for Ornlg, a complexation must occur with one of the nonbonded oxygen atoms in the phosphate groups (0 ) in such a way that unfavorable steric interactions are present with the C-C base pairs, which have a larger propellor twist angle than T-T base pairs. An analogy is presented between peptide complexation with the phosphates and the neutralization of the phosphate groups by methylation, which is known to lead to parallel duplexes with T-T base pairs (for both the 5 and j?P configurations) and C-C base pairs (only for the SP configuration). iKtrallel DNA duplexes, in which the 5' -* 3' vectors in the backbones run in the same direction, have been reported for natural oligodeoxynucleotides under extreme conditions (e.g., a highly acidic medium; Sarma et al., 1986), or for modified oligodeoxynucleotides. For instance, recently it was reported that, in the stem of hairpin structures with an artificial 3'-3' or 5'-5' linkage, a parallel arrangement of the strands can be forced (Germann et al., 1989). Also, the duplexes between oligodeoxynucleotides with -oriented bases and natural DNA are found to be parallel (Morvan et al., 1987;Thuong et al., 1987). Spontaneous formation of parallel duplexes has been found for phosphate-methylated pyrimidine oligomers (Koole et al., 1986(Koole et al., , 1987Quaedflieg et al., 1990a). Methylation of the phosphate groups leads to slim, right-handed duplexes with pyrimidine-pyrimidine base pairs, due to the elimination of interstrand phosphate-phosphate charge repulsions. For phosphate-methylated thymidine oligomers (dT", = 2-8) with thymine-thymine (T-T) base pairs, the configuration of the chiral phosphorus atom in the methyl phosphotriester group does not influence the duplex stability (Koole et al., 1987), even though for the SP configuration the methyl points into the solvent while for the RP configuration the methyl group is located in the groove of the helix (van Genderen et al., 1987a). However, for the phosphate-methylated nucleotides d(CpC) and d(TpC), miniduplexes with cytosine-cytosine (C-C) base pairs (and in the latter case also a T-T base pair) are formed exclusively for the SP configuration (Koole et al., 1988;Quaedflieg et al., 1990a). Molecular mechanics calculations have shown that the C-C base pair has a considerably larger propellor twist angle ...

show abstract

“…For methylphosphonate T n and poly(rA), the maximum T m value is reached for n = 4 (deviation from the natural helical structure). Hybridization between self-complementary phosphatemethylated DNA's may be in competition with parallel C-C duplexes for S P chirality of phosphorus, not with the R P chirality, and with parallel T-T duplexes for both S P and R P chiralities [12].…”

Section: Synthesis and Characterization Of Phosphatemethylated Dnamentioning

confidence: 99%

A conformational B-Z DNA study monitored with phosphatemethylated DNA as a model for epigenetic dynamics focused on 5-(hydroxy)methylcytosine

Buck¹

2013

JBPC

View full text Add to dashboard Cite

This study was directed on the B-into Z-DNA isomerization with alternating CG sequences monitored with artificial DNA model-systems based on methylation of the phosphate backbone. The chemical concept for this transition wherein shielding of the oxygen anions of the backbone phosphates plays an essential role, resulted in the preparation of the phosphatemethylated d(CpG). Even on this primitive level of only two base pair long, the B-Z conformational aspects of this selfcomplementary duplex could be described in solution with nuclear magnetic resonance (NMR) and circular dichroism (CD) measurements. The exclusivity of this choice became clear after synthesizing phosphatemethylated DNA with longer alternating CG fragments. It could be shown that conflicting conformational effects of the CG and GC fragments resulted in an overall B structure of the phosphatemethylated tetramer d(C P G P C P G). From our model considerations, it is clear that the internal stress introduced by the alternating CG sequences will be promoted by a complete shielding of the phosphate backbone. Elimination of this effect may be realized by a site-specific phosphate shielding. The role of the anti-syn isomerization of G in the CG fragments is clarified by methylation of the phosphate group. This anti-syn transition is absent in corresponding methylphosphonates, suggesting an exclusive role for base-backbone coordination via hydrogen bonding. In addition, we propose that the Binto Z-DNA interconversion may offer a mechanistic view for differences in dynamics between cytosine and its epigenetic derivative 5-methylcytosine. This mechanism has been extended to the demethylation of 5-methylcytosine and the exchange of information between the new epigenetic base, 5-hydroxymethylcytosine and the DNA backbone via an intramolecular phosphorylation. The role of 5-hydroxymethylcytosine in Alzheimer disease has been briefly discussed. In our opinion, this study can be considered as a new dynamic concept for epigenetics based on the dynamics of the B-Z transition in natural and phosphatemethylated DNA.

show abstract

A parallel right-handed duplex of the hexamer d(TpTpTpTpTpT) with phosphate triester linkages

Cited by 45 publications

References 0 publications

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

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

Peptide-induced parallel DNA duplexes for oligopyrimidines. Stereospecificity in complexation for oligo(L-lysine) and oligo(L-ornithine)

A conformational B-Z DNA study monitored with phosphatemethylated DNA as a model for epigenetic dynamics focused on 5-(hydroxy)methylcytosine

Contact Info

Product

Resources

About