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Download Antisense Research and Application by S. T. Crooke (auth.), Stanley T. Crooke M.D., Ph.D. (eds.) PDF

By S. T. Crooke (auth.), Stanley T. Crooke M.D., Ph.D. (eds.)

Antisense expertise may end up in dramatic alterations within the remedy of many illnesses and should supply instruments to dissect pharmacological strategies and to verify the jobs of assorted genes. during this quantity, growth within the realizing of antisense expertise and its use in growing new medicines is mentioned. strength caveats, pitfalls and barriers of the know-how also are awarded. within the following few years the speed at which new molecular pursuits can be pointed out increases exponentially because the sequencing of the human genome and of alternative genomes proceeds.

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These structures play crucial roles in a variety of functions. They are used to provide additional stability for RNA and as recognition motifs for a number of proteins, nucleic acids, and ribonucleoproteins that participate in the intermediary metabolism and activities of RNA species. Thus, given the potential general activity of the mechanism, it is surprising that occupancy-based disruption RNA has not been more extensively exploited. As an example, we designed a series of oligonucleotides that bind to the important stem loop present in all RNA species in HIV, the TAR element.

In 18 S. T. CROOKE one study, a larger molecular weight radioactive material was observed in urine, but not fully characterized (AGRAWAL et al. 1991). Clearly, the potential for conjugation reactions and extension of oligonucleotides via these drugs serving as primers for polymerases must be explored in more detail. In a very thorough study, 20 nucleotide phosphodiester and phosphorothioate oligonucleotides were administered intravenously at a dose of 6mg/kg to mice. The oligonucleotides were internally labeled with 3H-CH3 by methylation of an internal deoxycytidine residue using Hhal methylase and S-(3H) adenosylmethionine (SANDS et al.

1995). Clearly, much more work is required before definitive conclusions can be drawn. Phosphorothioate oligonucleotides can interact with nucleic acid binding proteins such as transcription factors and single-strand nucleic acid binding proteins. However, very little is known about these binding events. Additionally, it has been reported that phosphorothioates bind to an 80-KDa membrane protein that was suggested to be involved in cellular uptake processes (LaKE et al. 1989). However, again, little is known about the affinities, sequence or structure specificities of these putative interactions.

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