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
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 Back-bone 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 B-conformation, 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 After the HIV study was retracted, the overall results concerning the phosphate-methylated RNAs were published without mentioning Buck’s initial proof of concept and his contributions.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.
References
[1]
Quaedflieg, P.J.L.M., van der Heiden, A.P., Koole, L.H., van Genderen, M.H.P., Coenen, A.J.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.
[2]
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 Phosphate-Methylated RNA Dinucleotides. Journal of Organic Chemistry, 56, 5846-5859. http://dx.doi.org/10.1021/jo00020a028
[3]
Quaedflieg, P.J.L.M. (1993) Synthesis and Structural Aspects of Backbone-Modified Nucleic Acids. Thesis University of Leiden.
[4]
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. Implications of Phosphate Shielding for the Isomerization of B-DNA into Z-DNA. Recueil Travaux Chimiques des Pays-Bas, 108, 421-423.
http://dx.doi.org/10.1002/recl.19891081107
[5]
Buck, H.M., Koole, L.H., van Genderen, M.H.P., Smit, L., Geelen, J.L.M.C., Jurriaans, S. and Goudsmit, J. (1990) Phosphate-Methylated DNA Aimed at HIV-1 RNA Loops and Integrated DNA Inhibits Viral Infectivity. Science, 248, 208-211. http://dx.doi.org/10.1126/science.2326635
[6]
Moody, H.M., Quaedflieg, P.J.L.M., Koole, L.H., van Genderen, M.H.P., Buck, H.M., Smit, L., Jurriaans, S., Geelen, J.L.M.C. and Goudsmit, J. (1990) Retraction: Inhibition of HIV-1 Infectivity by Phosphate-Methylated DNA. Science, 250, 125. http://dx.doi.org/10.1126/science.2218505
[7]
Buck, H.M. (1996) Phosphate-Methylated DNA: A Unique Oligodeoxynucleotide as Compared with Other Modified DNAs. Proceedings of the Koninklijke Nederlandse Akademie van Wetenschappen, 99, 145-153.
[8]
Vester, B. and Wengel, J. (2004) LNA (Locked Nucleic Acid): High-Affinity Targeting of Complementary RNA and DNA. Biochemistry, 43, 13233-13241. http://dx.doi.org/10.1021/bi0485732
[9]
Brown, D., Arzumanov, A.A., Turner, J.J., Stetsenko, D.A., Lever, A.M.L. and Gait, M.J. (2005) Antiviral Activity Steric-Block Oligonucleotides Targeting the HIV-1 Trans-Activation Response and Packaging Signal Stem-Loop RNAs. Nucleosides, Nucleotides and Nucleic Acids, 24, 393-396. http://dx.doi.org/10.1081/NCN-200059813
[10]
Jakobsen, M.R., Haasnoot, J., Wengel, J., Berkhout, B. and Kjems, J. (2007) Efficient Inhibition by LNA Modified Antisense Oligonucleotides and DNAzymes Targeted to Functionally Selected Binding Sites. Retrovirology, 4, 29.
http://dx.doi.org/10.1186/1742-4690-4-29
[11]
Kanasty, R., Dorkin, J.R., Vegas, A. and Anderson, D. (2013) Delivery Materials for siRNA Therapeutics. Nature Materials, 12, 967-977. http://dx.doi.org/10.1038/nmat3765
[12]
Buck, H.M. (2015) The Risk of the Preparation of Artificial DNAs via an Interrupted Automated Solid-Phase Triester Method. Nucleosides, Nucleotides and Nucleic Acids, 34, 400-415. http://dx.doi.org/10.1080/15257770.2015.1006774
[13]
Paul, S., Roy, S., Monfregola, L., Shang, S., Shoemaker, R. and Caruthers, M.H. (2015) Oxidative Substitution of Borane Phosphonate Diesters as a Route to Post-Synthetically Modified DNA. Journal of the American Chemical Society, 137, 3253-3264. http://dx.doi.org/10.1021/ja511145h
[14]
Buck, H.M. (2013) A Conformational B-Z Study Monitored with Phosphatemethylated DNA as a Model for Epigenetic Dynamics Focused on 5-(Hydroxy)methylcytosine. Journal of Biophysical Chemistry, 4, 37-46.
http://dx.doi.org/10.4236/jbpc.2013.42005
[15]
Koole, L.H., Moody, H.M., Broeders, N.L.H.L., Quaedflieg, P.J.L.M., Kuijpers, W.H.A., van Genderen, M.H.P., Coenen, A.J.J.M., van der Wal, S. and Buck, H.M. (1989) Synthesis of Phosphate-Methylated DNA Fragments Using 9-Fluorenylmethoxycarbonyl as Transient Base Protecting Group. Journal of Organic Chemistry, 54, 1657-1664.
http://dx.doi.org/10.1021/jo00268a030
[16]
Marugg, J.E., Nielsen, J., Dahl, O., Burik, A., van der Marel, G.A. and van Boom, J.H. (1987) (2-Cyano-1,1-dimethyl-ethoxy)bis(diethylamino)phosphine: A Convenient Reagent for the Synthesis of DNA Fragments. Recueil des Travaux Chimiques des Pays-Bas, 106, 72-76. http://dx.doi.org/10.1002/recl.19871060302
[17]
Kuijpers, W.H., Huskens, J., Koole, L.H. and van Boeckel, C.C.A. (1990) Synthesis of Well-Defined Phosphate-Methylated DNA Fragments in Methanol as Deprotecting Agent: The Application of Potassium Carbonate in Methanol as Deprotecting Agent. Nucleic Acids Research, 18, 5197-5205. http://dx.doi.org/10.1093/nar/18.17.5197
[18]
Davis, P.W., Adamiak, R.W. and Tinoco Jr., I. (2004) Z-RNA: The Solution NMR Structure of r(CGCGCG). Biopoymers, 29, 109-122. http://dx.doi.org/10.1002/bip.360290116
[19]
Popenda, M., Milecki, J. and Adamiak, R.W. (2004) High Salt Solution of a Left-Handed RNA Double Helix. Nucleic Acids Research, 32, 4044-4054. http://dx.doi.org/10.1093/nar/gkh736
[20]
Adamiak, D.A., Rypniewski, W.R., Milecki, J. and Adamiak, R.W. (2001) The 1.19Å X-Ray Structure of 2’-O-Me (CGCGCG)2 Duplex Shows Dehydrated RNA with 2-Methyl-2,4-pentanediol in the Minor Groove. Nucleic Acids Research, 29, 4144-4153. http://dx.doi.org/10.1093/nar/29.20.4144
[21]
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 Mini-Duplex Exclusively for the S Configuration at Phosphorus. Journal of Organic Chemistry, 55, 122-127.
http://dx.doi.org/10.1021/jo00288a025
[22]
Marky, L.A. and Breslauer, J. (1987) Calculating Thermodynamic Data for Transitions of Any Molecularity from Equilibrium Melting Curves. Biopolymers, 26, 1601-1620. http://dx.doi.org/10.1002/bip.360260911
[23]
Van Genderen, M.H.P., Koole, L.H., Aagaard, O.M., van Lare, C.E.J. and Buck, H.M. (1987) Molecular Mechanics Studies of Parallel and Antiparallel Phosphate-Methylated DNA. Biopolymers, 26, 1447-1461.
http://dx.doi.org/10.1002/bip.360260902
[24]
Schreiner, P.R., Chernish, L.V., Gunchenko, P.A., Tikhonchuk, E.Y., Hausman, H., Serafin, M., Schlecht, S., Dahl, J.E.P., Carlson, R.M.K. and Fokin, A.A. (2011) Overcoming Lability of Extremely Long Alkane Carbon-Carbon Bonds through Dispersion Forces. Nature, 477, 308-311. http://dx.doi.org/10.1038/nature10367
[25]
Wagner, J.P. and Schreiner, P.R. (2014) Nature Utilizes Unusual High London Dispersion Interactions for Compact Membranes of Molecular Ladders. Journal of Chemical Theory and Computation, 10, 1353-1358.
http://dx.doi.org/10.1021/ct5000499
[26]
Koole, L.H., van Genderen, M.H.P., Reiniers, R.G. and Buck, H.M. (1987) Enhanced Stability of a Watson & Crick DNA Duplex Structure by Methylation of the Phosphate Group. Proceedings of the Koninklijke Nederlandse Akademie van Wetenschappen, 90, 41-46.
[27]
Pless, R.C. and Ts’o, P.O.P. (1977) Duplex Formation of Nonionic Oligo(deoxythymidylate) Analogue [Heptadeoxythymidilyl-(3’-5’)-deoxythymidine heptaethyl ester d[d(TP(Et)]7T] with Poly-(Deoxyadenylate). Evaluation of the Electrostatic Interaction. Biochemistry, 16, 1239-1250. http://dx.doi.org/10.1021/bi00625a033
[28]
Van Genderen, M.H.P., Koole, L.H. and Buck, H.M. (1989) Hybrization of Phosphate-Methylated DNA and Natural Oligonucleotides. Implications for Protein-Induced DNA Duplex Destabilization. Recueil des Travaux Chimiques des Pays-Bas, 108, 28-35. http://dx.doi.org/10.1002/recl.19891080106
[29]
Moody, M.R., van Genderen, M.H.P. and Buck, H.M. (1990) Thermodynamics of Polymolecular Duplexes between Phosphate-Methylated DNA and Natural DNA. Biopolymers, 30, 609-618. http://dx.doi.org/10.1002/bip.360300513
[30]
Van Genderen, M.H.P. (1989) Structure and Stability of Phosphate-Methylated DNA Duplexes. Master’s Thesis, Eindhoven University of Technology, Eindhoven.
[31]
Buck, H.M. (2004) The Chemical and Biochemical Properties of Methyl Phosphotriester DNA. Nucleosides, Nucleotides and Nucleic Acids, 23, 1833-1847. http://dx.doi.org/10.1081/NCN-200040620
[32]
Ramakrishnan, B. and Viswamitra, M.A. (1988) Crystal and Molecular Structure of the Ammonium Salt of the Dinucleoside Monophosphate d(CPG). Journal of Biomolecular Structure and Dynamics, 6, 511-523.
http://dx.doi.org/10.1080/07391102.1988.10506504
[33]
Han, F., Watt, W., Duchamp, D., Callahan, L., Kézdy, F.J. and Agarwal, K. (1990) Molecular Structure of Deoxycytidyl-3’-methylphosphonate (RP) 5’-Deoxyguanidine, d[CP(CH3)G]. A Neutral Dinucleotide with Watson-Crick Base Pairing and a Right Handed Helical Twist. Nucleic Acids Research, 18, 2759-2767.
http://dx.doi.org/10.1093/nar/18.9.2759
[34]
Wang, A.H.J., Quigley, G.J., Kolpak, F.J., Crawford, J.L., van Boom, J.H., van der Marel, G. and Rich, A. (1979) Molecular Structure of a Left-Handed Double Helical DNA Fragment at Atomic Resolution. Nature, 282, 680-686.
http://dx.doi.org/10.1038/282680a0
[35]
Tollin, P., Walker, R.T. and Wilson, H.R. (1984) Is There Sometimes T-T Wobble Pairing in Thymidylyl-3’,5’? Nucleic Acids Research, 12, 8345-8347. http://dx.doi.org/10.1093/nar/12.22.8345
[36]
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.
http://dx.doi.org/10.1021/ja00247a015
[37]
Cruse, W.B.T., Egert, E., Kennard, O., Sala, G.B., Salisbury, S.A. and Viswamitra, M.A. (1983) Self Base Pairing in a Complementary Deoxydinucleoside Monophosphate Duplex Crystal and Molecular Structure of Deoxycytidylyl-(3’-5’)-deoxyguanosine. Biochemistry, 22, 1833-1839. http://dx.doi.org/10.1021/bi00277a014
[38]
Young, D.W. and Wilson, H.R. (1975) The Crystal and Molecular Structure of 2’-Deoxycytidine. Acta Crystallographica Section B, 31, 961-965. http://dx.doi.org/10.1107/S0567740875004281
[39]
Sarma, M.H., Gupta, G. and Sharma, R.H. (1986) A Cytosine-Cytosine Base Paired Parallel DNA Double Helix with Thymine-Thymine Bulges. FEBS Letters, 205, 223-229. http://dx.doi.org/10.1016/0014-5793(86)80902-4
[40]
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.
[41]
Buck, H.M. (2011) DNA Systems for B-Z Transition and Their Significance as Epigenetic Model: The Fundamental Role of the Methyl Group. Nucleosides, Nucleotides and Nucleic Acids, 30, 918-944.
http://dx.doi.org/10.1080/15257770.2011.620580
[42]
Wang, S., Long, Y., Wang, J., Ge, Y., Guo, P., Liu, Y., Tian, T. and Zhou, X. (2014) Systematic Investigations of Different Cytosine Modifications on CPG Dinucleotide Sequences: The Effect on the B-Z Transition. Journal of the American Chemical Society, 136, 56-59. http://dx.doi.org/10.1021/ja4107012
[43]
Raiber, E.-A., Murat, P., Chirgadze, D.Y., Beraldi, D., Luisi, B.F. and Balasubramanian, S. (2015) 5-Formylcytosine Alters the Structure of the DNA Double Helix. Nature Structural & Molecular Biology, 22, 44-49.
http://dx.doi.org/10.1038/nsmb.2936
[44]
Aartsma-Rus, A. and van Ommen, G.J.B. (2007) Antisense-Mediated Exon Skipping: A Versatile Tool with Therapeutic and Research Applications. RNA, 13, 1609-1624. http://dx.doi.org/10.1261/rna.653607
[45]
Buck, H.M. (2015) Retracted HIV Study Provides New Information about the Status of the in Vitro Inhibition of DNA Replication by Backbone Methylation. Journal of Biophysical Chemistry, 6, 29-34.
http://dx.doi.org/10.4236/jbpc.2015.61003