Abstract
At the moment, we see a great interest for application of Anti Sense Oligonucleotides (ASOs) 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, we selected synthetically (short) phosphate-methylated 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 way in public health as is clearly shown in the treatment of (progressive) neurological diseases. We focus specifically on the past, present and future of the phosphate-methylated oligonucleotides, illustrated with different research studies in chemistry and biophysics. A new field of application of modified DNAs is based on interactive improvements of sensitivity and specificity of nanowire field effect transistor gene chip by designing phosphate-methylated DNA as probe.
Highlights
We see a great interest for application of Anti Sense Oligonucleotides (ASOs) in order to regulate the expression of genes related to certain diseases
It was concluded that there is an exclusive selection in hybridization affinity with natural DNA and RNA
It is known that Anti Sense Oligonucleotides (ASOs) are synthetically prepared single-stranded deoxynucleotide sequences that can block the expression of specific target genes via complementary hybridization [1]
Summary
It is known that Anti Sense Oligonucleotides (ASOs) are synthetically prepared (short) single-stranded deoxynucleotide sequences that can block the expression of specific target genes via complementary hybridization [1]. The published (bio)chemical and physical-chemical data demonstrate a number of exclusive properties These oligonucleotides have shown enhanced duplex stability due to the decrease in electrostatic repulsion between the complementary strands. Symmetry related molecules pack in such a way that the cytosine base stacks on cytosine and guanine base on guanine This demonstrates that alternating d (CPG) sequences have the ability to adopt the left handed Z-DNA structure even at the dimer level. A more elaborate study was published before with the hexamer by Wang et al [4] This situates the molecular structure of the corresponding phosphate-methylated dimer duplex measured in solution in a unique position. Besides the shielding of the phosphates and the characteristics of the sugar puckering for a left-handed natural d (CPG) duplex, the influence of coordination in solution and crystal state is of importance for understanding the dynamics of the B-Z. We focus on the past, present and future of the phosphate-methylated oligonucleotides, illustrated with different research studies in chemistry and biophysics
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