The Biochemical Impact by Covalent Shielding of the Anionic Oxygen of the Phosphate Group in DNA and RNA as Methylated Phosphotriester Linkage on the Inhibition of DNA Duplication and on HIV-1 RNA Viral Infectivity Has Been Seriously Overlooked
With the help of model experiments, we are able to offer a detailed proposal for the inhibition of DNA duplication and no inhibition of RNA viral infectivity. As a backbone, we introduced methyl phosphotriester (MPTE). Duplex formation according to the traditional Watson and Crick base-pairing: [(MPTE)n−1 DNA] * DNA and [(MPTE)n−1 DNA] * RNA, where n = number of DNA and RNA bases. However, in the latter case, inhibition is obtained by reduction of the number of MPTE linkages, as is confirmed with model experiments and under biological conditions with micro (mi)RNA substrates. The latter results have recently been published. One or more single MPTEs are disseminated over different places of DNA without neighbour MPTEs (Prof. Wen-Yih Chen and his group, Taiwan).
References
[1]
Quaedflieg, P.J.L.M., Koole, L.H., Van Genderen, M.H.P. and Buck, H.M. (1989) A Structural Study of Phosphate-Methylated d(CpG)n and d(GpC)n DNA Oligomers. Implication of Phosphate Shielding for the Isomerization of B-DNA into Z-DNA. Recueil des Travaux Chimiques des Pays-Bas, 108, 421-423.
https://doi.org/10.1002/recl.19891081107
[2]
Yi, J., Yeou, S. and Lee, N.K. (2022) DNA Bending Force Facilitates Z-DNA Formation under Physiological Salt Conditions. Journal of the American Chemical Society, 144, 13137-13145. https://doi.org/10.1021/jacs.2c02466
[3]
Buck, H.M. (2020) Phosphate-Methylated Oligonucleotides Past, Present and Future. Journal of Biophysical Chemistry, 11, 27-42.
https://doi.org/10.4236/jbpc.2020.113003
[4]
Moody, H.M., Van Genderen, M.H.P., Koole, L.H., Kocken, H.J.M., Meijer, E.M. and Buck, H.M. (1989) Regiospecific Inhibition of DNA Duplication by Antisense Phosphate-Methylated Oligodeoxynucleotides. Nucleic Acids Research, 17, 4769-4782.
https://doi.org/10.1093/nar/17.12.4769
[5]
Koole, L.H., Van Genderen, M.H.P. and Buck, H.M. (1987) A Parallel Right-Handed Duplex of the Hexamer d(TpTpTpTpTpT) with Phosphate Triester Linkages. Journal of the American Chemical Society, 109, 3916-3921.
https://doi.org/10.1021/ja00247a015
[6]
Quaedflieg, P.J.L.M., Broeders, N.L.H.L., Koole, L.H., Van Genderen, M.H.P. and Buck, H.M. (1990) Conformation of the Phosphate-Methylated DNA Dinucleotides d(CpC) and d(TpC). Formation of a Parallel Miniduplex Exclusively for the S Configuration at Phosphorus. Journal of Organic Chemistry, 55, 122-127.
https://doi.org/10.1021/jo00288a025
[7]
Quaedflieg, P.J.L.M., Van der Heiden, A.P., Koole, L.H., Van Genderen, M.H.P., Coenen, A.J.M., Van der Wal, S. and Buck, H.M. (1990) Synthesis and Conformation of Phosphate-Methylated r(CpU) and r(ApU). Formation of a Parallel Right-Handed Duplex for Sp r(CpU). Proceedings of the Koninklijke Nederlandse Akademie van Wetenschappen, 93, 33-38.
[8]
Quaedflieg, P.J.L.M., Van der Heiden, A.P., Koole, L.H., Coenen, A.J.J.M., Van der Wal, S. and Meijer, E.M. (1991) Synthesis and Conformational Analysis of Phosphatemethylated RNA Dinucleosides. Journal of Organic Chemistry, 56, 5846-5859.
https://doi.org/10.1021/jo00020a028
[9]
Van Genderen, M.H.P., Hilbers, M.P., Koole, L.H. and Buck, H.M. (1990) Peptide-Induced Parallel DNA Duplexes for Oligopyrimidines. Stereospecificity in Complexation for Oligo(L-lysine) and Oligo(L-Ornithine). Biochemistry, 29, 7838-7845.
https://doi.org/10.1021/bi00486a009
[10]
Van Genderen, M.H.P., Koole, L.H. and Buck, H.M. (1989) Hybridization of Phosphate-Methylated DNA and Natural Oligonucleotides. Implications for Protein-Induced DNA Duplex Stabilization. Recueil des Travaux Chimiques des Pays-Bas, 108, 28-32.
https://doi.org/10.1002/recl.19891080106
[11]
Van Genderen, M.H.P. (1989) Structure and Stability of Phosphate-Methylated DNA Duplexes: Model Systems for Specific DNA-Protein Interaction and Conformational Transmission. Ph.D. Thesis, University of Technology, Eindhoven, 186 p.
[12]
Van Genderen, M.H.P., Koole, L.H. and Buck, H.M. (1988) Duplex Stability of Hybrids between Phosphate-Methylated DNA and Natural RNA. Proceedings of the Koninklijke Nederlandse Akademie van Wetenschappen, 91, 53-57.
[13]
Buck, H.M., Koole, L.H., Van Genderen, M.H.P., Smit, L., Geelen, J.L.M.C. and Goudsmit, J. (1990) Phosphate-Methylated DNA Aimed at HIV-1 RNA Loops and Integrated DNA Inhibits Viral Infectivity. Science, 248, 208-212.
https://doi.org/10.1126/science.2326635
[14]
Wang, P.-H., Jia, T.Z., Chang, C.-W., Tan, B.C.-W., Chi, Y.-H. and Chen, W.-Y. (2022) Sensitive and Specific MicroRNA in Situ Hybridization Using Partially Methylated Phosphotriester Antisense DNA Probes. GEN Biotechnology, 1, 447-455.
https://doi.org/10.1089/genbio.2022.0023
[15]
Jorgensen, S., Baker, A., Moller, S., et al. (2010) Robust One-Day in Situ Hybridization Protocol for Detection of MicroRNAs in Paraffin Sample Using LNA Probes. Methods, 52, 375-381. https://doi.org/10.1016/j.ymeth.2010.07.002
[16]
Beaucage, L. and Caruthers, M.H. (1981) Deoxynucleoside Phosphoramidites—A New Class of Key Intermediates for Deoxypolypolynucleotide Synthesis. Tetrahedron Letters, 22, 1859-1862. https://doi.org/10.1016/S0040-4039(01)90461-7
[17]
Koole, L.H., Moody, H.M., Broeders, N.L.H., Quaedfkieg, P.J.L.M., Kuijpers, W.H.A., Van Genderen, M.H.P., Coenen, A.A.J.M., Van der Wal, S. and Buck, H.M. (1989) Synthesis of Phosphate-Methylated DNA Fragments Using 9-Florenyl-Methoxycarbonyl as Transient Base Protecting Group. Journal of Organic Chemistry, 54, 1657-1664. https://doi.org/10.1021/jo00268a030
[18]
Miller, P.S., Tang, K.N., Kondo, N.S. and Ts’o, P.O.P. (1971) Conformation and Interaction of Dinucleoside Mono- and Diphosphates. V. Synthesis and Properties of Adenine and Thymine Nucleoside Alkyl Phosphotriesters, the Neutral Analogs of Dinucleoside Monophosphates. Journal of the American Chemical Society, 93, 6657-6665. https://doi.org/10.1021/ja00753a054
