Antisense oligonucleotides chemistry

Aboul-Fadt, T. 2005. Antisense oligonucleotides the state of the art. Current Medicinal Chemistry 12(19), 2193-2214. 

Example 56 the Isis Pharmaceutical group in their extensive investigations of antisense oligonucleotides as therapeutics has described the synthesis of 3 -C-methylene nucleoside phosphonoamidites for the new backbone modification of oligonucleotides [90]. This paper gives good insight into tricoordinate phosphorus and related H-phosphonate chemistry in the service of nucleotide synthesis. 

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. 

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