- 2′-Fluoro-c-di-GMP as an oral vaccine adjuvant
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Bis-(3′-5′)-cyclic dimeric 2′-deoxy-2′-fluoroguanosine monophosphate (2′-F-c-di-GMP) was synthesized through the modified H-phosphonate chemistry. Oral immunization of C57BL/6 mice with Helicobacter pylori cell-free sonicate extract adjuvanted with 2′-F-c
- Li, Jia,Lee, Rhonda Kuo,Chen, Wangxue,Yan, Hongbin
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- COMPOSITIONS AND METHODS FOR ACTIVATING "STIMULATOR OF INTERFERON GENE"-DEPENDENT SIGNALLING
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The present invention provides highly active cyclic-di-nucleotide (CDN) immune stimulators that activate DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the CDNs of the present invention are provided in the form of a composition comprising one or more cyclic purine dinucleotides induce human STING-dependent type I interferon production, wherein the cyclic purine dinuclotides present in the composition are 2'- or 3'-mono-fluoro substituted, or 2'3'-di-fluoro substituted mixed linkage 2',5' - 3',5' CDNs.
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Paragraph 00492; 00493
(2017/05/17)
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- COMPOSITIONS AND METHODS FOR ACTIVATING "STIMULATOR OF INTERFERON GENE" -DEPENDENT SIGNALLING
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The present invention provides highly active cyclic-di-nucleotide (CDN) immune stimulators that activate DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes), In particular, the CDNs of the present invention a
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Paragraph 00383; 00384
(2016/09/26)
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- Uniformly modified 2'-deoxy-2'-fluoro phosphorothioate oligonucleotides as nuclease-resistant antisense compounds with high affinity and specificity for RNA targets
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'Uniformly' modified phosphodiester or phosphorothioate oligonucleotides incorporating 2'-deoxy-2'-fluoroadenosine, -guanosine, -uridine, and - cytidine, reported herein for the first time, when hybridized with RNA afforded consistent additive enhancement of duplex stability without compromising base-pair specificity. CD spectra of the 2'-deoxy-2'-fluoro- modified oligonucleotides hybridized with RNA indicated that the duplex adopts a fully A-form conformation. The 2'-deoxy-2'-fluoro-modified oligonucleotides in phosphodiester form were not resistant to nucleases; however, the modified phosphorothioate oligonucleotides were highly nuclease resistant and retained exceptional binding affinity to the RNA targets. The stabilizing effects of the 2'-deoxy-2'-fluoro modifications on RNA-DNA duplexes were shown to be superior to those of the 2'-O-methylribo substitutions. RNA hybrid duplexes with uniformly 2'-deoxy-2'-fluoro-modified oligonucleotides did not support HeLa RNase H activity; however, incorporation of the modifications into 'chimeric' oligonucleotides has been shown to activate mammalian RNase H. 'Uniformly' modified 2'-deoxy-2'-fluoro phosphorothioate oligonucleotides afforded antisense molecules with (1) high binding affinity and selectivity for the RNA target and (2) stability toward nucleases.
- Kawasaki,Casper,Freier,Lesnik,Zounes,Cummins,Gonzalez,Cook
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p. 831 - 841
(2007/10/02)
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