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”, i...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 After the HIV study was retracted, the overall results concerning the phosphate-methylated RNAs were published without mentioning Buck’s initial proof of concept and his contributions.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.展开更多
At the moment<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">,</span></span></span><span>...At the moment<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">,</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> we see a great interest for application of Anti Sense Oligonucleotides</span><span style="font-family:Verdana;"> (ASOs) </span><span style="font-family:Verdana;">in order to regulate the expression of genes related to certain diseases. These nucleotides obtained a number of fascinating properties by means of chemical manipulation of natural DNA and RNA under conservation of Watson-Crick base-pairing. About 35 years ago for our research in this field</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">,</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> we selected synthetically (short) </span><i><span style="font-family:Verdana;">phosphate-methylated</span></i><span style="font-family:Verdana;"> DNA and RNA. It was concluded that there is an exclusive selection in hybridization affinity with natural DNA and RNA. These (bio)chemical and physical-chemical properties are extensively published. ASOs have found their </span><span style="font-family:Verdana;">way in public health as is clearly shown in the treatment of (progressive)</span><span style="font-family:Verdana;"> neurological diseases. We focus specifically on the past, present and future of the </span><span style="font-family:Verdana;">phosphate-methylated oligonucleotides, illustrated with different research</span><span style="font-family:Verdana;"> stu</span><span style="font-family:Verdana;">dies in chemistry and biophysics. A new field of application of modified</span><span style="font-family:Verdana;"> DNAs is based on interactive improvements of sensitivity and specificity of nanowire field effect transistor gene chip by designing phosphate-methylated DNA as probe.</span></span></span></span>展开更多
文摘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.
文摘At the moment<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">,</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> we see a great interest for application of Anti Sense Oligonucleotides</span><span style="font-family:Verdana;"> (ASOs) </span><span style="font-family:Verdana;">in order to regulate the expression of genes related to certain diseases. These nucleotides obtained a number of fascinating properties by means of chemical manipulation of natural DNA and RNA under conservation of Watson-Crick base-pairing. About 35 years ago for our research in this field</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">,</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> we selected synthetically (short) </span><i><span style="font-family:Verdana;">phosphate-methylated</span></i><span style="font-family:Verdana;"> DNA and RNA. It was concluded that there is an exclusive selection in hybridization affinity with natural DNA and RNA. These (bio)chemical and physical-chemical properties are extensively published. ASOs have found their </span><span style="font-family:Verdana;">way in public health as is clearly shown in the treatment of (progressive)</span><span style="font-family:Verdana;"> neurological diseases. We focus specifically on the past, present and future of the </span><span style="font-family:Verdana;">phosphate-methylated oligonucleotides, illustrated with different research</span><span style="font-family:Verdana;"> stu</span><span style="font-family:Verdana;">dies in chemistry and biophysics. A new field of application of modified</span><span style="font-family:Verdana;"> DNAs is based on interactive improvements of sensitivity and specificity of nanowire field effect transistor gene chip by designing phosphate-methylated DNA as probe.</span></span></span></span>
