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Chemistry and Biochemistry of 2', 5'-Oligoadenylate-Based Antisense Strategy

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This review describes the application of a natural defense mechanism to develop effective agents for The post-transcriptional control of gene expression. 2-5A is a unique 2',5'-phosphodiester bond linked oligoadenylate, (pp)p5'A2'(p5'A)n , that is elaborated in virus-infected interferon-treated cells. The 2-5A System is an RNA degradation pathway that is an important mechanistic component of interferon's action against certain viruses. It may also play a role in the anticellular effects of interferon and in general RNA decay. A major player in the 2-5A-system is the latent and constitutive 2-5A-dependent ribonuclease (RNase L) which upon activation by 2-5A, degrades RNA. This RNase L enzyme can be recruited for antisense therapeutics by linking it to an appropriate oligonucleotide targeted to a chosen RNA. Syntheses of 2-5A, its analogues, 2-5A-antisense, and its modifications are detailed herein. Applications of 2-5A-antisense to particular targets such as HIV, PKR, chronic myelogenous leukemia, telomerase, and respiratory syncytical Virus is described.
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Keywords: 2-5A-ANTI-SENSE(2-5A-AS); Apoptosis; Condensation; Coupling agents; Oligoadenylate-Based Antisense; Ribonucleases; Syncytial Virus

Document Type: Review Article

Publication date: 01 August 2001

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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