Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1993-10-14
1998-11-17
Chambers, Jasemine C.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 231, 536 241, 536 243, 514 44, C12N 500, C12N 1500, C07N 1400, A61K 4800
Patent
active
058378529
ABSTRACT:
Novel capped oligonucleotides useful in treatment of influenza infection. A P! labeled cap-1 structure was used to analyze parameters of influenza virus endonuclease activity. This substrate was specifically cleaved by the influenza virus polymerase to yield a single capped 11-nucleotide fragment capable of directly priming transcription. An analysis of systematic truncations of this RNA substrate in cleavage, elongation, and binding reactions demonstrated that the minimum chain length required for cleavage was one nucleotide past the cleavage site. In contrast, the minimum chain length required for priming activity was found to be 9 nucleotides, while a chain length of at least 4 nucleotides was required for efficient binding. Based on these chain length requirements, the present inventors show that a pool of capped oligonucleotides--too short to prime transcription but long enough to bind with high affinity to the viral polymerase--are potent inhibitors of cap-dependent in vitro transcription.
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Chung Thomas D. Y.
Cianci Christopher W.
Colonno Richard J.
Hagen Moira
Krystal Mark
Bristol--Myers Squibb Company
Chambers Jasemine C.
Gaul Timothy J.
Milne Andrew
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