Antisense drugs structure

Antisense Approach This is a relatively new approach and it requires modifications to oligonucleotides that can bind to RNA and DNA (refer to Appendix 2 for a description of cell structure, genes, DNA, RNA, and proteins). The antisense drugs are used to stop transcriptional (from DNA) or translational (from RNA) pathways from proceeding, and so interfere with the process of disease. 

Figure 1 Molecular structure of examples of first- and second-generation antisense drugs.

With their structures only slightly reminiscent of natural oligonucleotides, peptide nucleic acids (PNAs) have had a significant impact on antisense drug development. Their synthesis... 

Fig. 8.4. First-generation generalized structures of natural DNA (phosphodiester) and three antisense oligonucleotide derivatives tested as antisense drugs. (Adapted from Agrawal S, Iyer RP. Perspectives in antisense therapeutics. Pharmacol Ther 1997 76 151-160 with permission.)...

There are two main approaches to discovering small molecule drugs the irrational approach or the more recent structured rational approach. Antisense, RNA interference, and chiral drugs are other drug discovery methodologies. 

A key to understanding antisense technol-t ogy is to consider it in a pharmacological context. It is essential to understand the structure, function, and metabolism of the receptors for these drugs. As with any of the class of dmgs, it is essential to consider the effects of antisense oligonucleotides in the context of dose-response curves. It is essential to consider the future in the context of advances in antisense biology and medicinal chemistry that result in improved pharmacological behaviors. 

Harborth J, Elbashir S M, et al. (2003). Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. Antisense Nucleic Acid Drug Dev. 13 83-105. 

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