A new and potent 2-5A analogue which does not require a 5′-polyphosphate to activate mouse L-cell RNase L

Torrence, Paul F.; Brózda, Danuta; Alster, D.; Pabuççuoğlu, Aysun; Lesiak, Krystyna

doi:10.1016/0166-3542(92)90061-9

Cited by 6 publications

(2 citation statements)

References 19 publications

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“…Structures of key 2-5A congeners particular chosen mRNA sequence which is then destroyed through localized activation of the latent 2-5A-dependent RNase L (Adah et al, 2001;Lesiak et al, 1993;Silverman et al, 2000;Torrence, 1999;Torrence et al, 1993;1997) ( Figure 8). The exact formulation of the linkage modality between the 2′,5′-oligoadenylate moiety and the antisense domain was dictated by knowledge of 2-5A SAR (Imai et al, 1982a(Imai et al, , 1982bJamoulle et al, 1984;Jamoulle et al, 1987;Kitade et al, 1989;1991;Krause et al, 1986;Sawai et al, 1983Sawai et al, , 1985Torrence et al, 1985Torrence et al, , 1984Torrence et al, , 1988Torrence et al, , 1992. Based on the foregoing, we have speculated (Torrence, 1999) that the 2-5A-antisense strategy would be able to compensate, in part at least, for the deficient interferon responses characteristic of RSV infections.…”

Section: Viruses and Interferons: Attack And Counterattackmentioning

confidence: 99%

The Quest for an Efficacious Antiviral for Respiratory Syncytial Virus

Torrence

Powell

2002

Antivir Chem Chemother

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Respiratory syncytial virus (RSV) continues as an emerging infectious disease not only among infants and children, but also for the immunesuppressed, hospitalized and the elderly. To date, ribavirin (Virazole) remains the only therapeutic agent approved for the treatment of RSV. The prophylactic administration of palivizumab is problematic and costly. The quest for an efficacious RSV antiviral has produced a greater understanding of the viral fusion process, a new hypothesis for the mechanism of action of ribavirin, and a promising antisense strategy combining the 2′-5′ oligoadenylate antisense (2-5A-antisense) approach and RSV genomics.

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Section: Viruses and Interferons: Attack And Counterattackmentioning

confidence: 99%

The Quest for an Efficacious Antiviral for Respiratory Syncytial Virus

Torrence

Powell

2002

Antivir Chem Chemother

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“…though the latter play a role in the biological activity of the (2'-5')oligo(adenylate) system, they can be replaced to a certain extent by modification elsewhere in the molecule [15]. Furthermore, it has been postulated that (A2'p5'),A may be rephosphorylated once it has entered the intact cell [l].…”

mentioning

confidence: 99%

Conformational analysis of 3′‐fluorinated A(2′‐5′)A(2′‐5′)A fragments

Boogaart

Kalinichenko

Podkopaeva

et al. 1994

European Journal of Biochemistry

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A one‐ and two‐dimensional NMR study has been performed on seven A(2′–5′)A(2′–5′)A fragments containing 9‐(3′‐fluoro‐3′‐deoxy‐β‐D‐xylofuranosyl)‐adenine (AF) or 3′‐fluoro‐3′‐deoxyadenosine (AF) residues at different positions, and on the corresponding monomers. A(2′–5′)A(2′–5′)A served as a reference compound. The fluoro substituent governs the conformation of the sugar ring: an AF residue displays mainly N‐type sugar and the ring is considerably flattened (øN∼ 30°) compared to AF residues (øS∼ 40°), which exhibit almost pure S‐type conformation. Moreover, in AF moieties the rotamer distribution around torsion angle γ (O5′‐C5′‐C4′‐C3′) and the base orientation are influenced to a large extent by the preseñce of the fluorine substituent. The sugar rings of nonfluorinated residues in the trimers appear rather flexible. A possible correlation between the conformational characteristics of the fluorinated fragments and their biological activity has been found: the fragments that meet the prerequisites for binding to RNase L indeed show enhanced binding to this endonuclease. Furthermore, substitution of the 3′‐OH group of the second residue by hydrogen or of the 3′‐OH group of the 2′‐terminal residue by fluorine or hydrogen results in increased resistance towards 2′–5′‐phosphodiesterase.

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The solid-phase synthesis of 2-5-linked oligoriboadenylates containing 8-bromoadenine

Lesiak

Uznański

Torrence

1997

Appl Biochem Biotechnol

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To increase the accessibility of 8-bromo-2',5'-oligoadenylates, we developed a synthesis of 2'-5'-linked oligoriboadenylates containing varying numbers of 8-bromoadenosine residues based on the use of a CPG-LCA solid support and the phosphoramidite approach. Although N6-benzoyl protection was satisfactory for incorporation of nonmodified adenine residues into 2',5'-oligonucleotides, the effective incorporation of 8-bromoadenine into such 2',5'-linked oligomers required use of a non acyl protecting group. Amidine protection of the purine exocyclic amino function proved compatible with all aspects of the phophoramidite approach and with the hydroxyl protection groups employed.

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A new and potent 2-5A analogue which does not require a 5′-polyphosphate to activate mouse L-cell RNase L

Cited by 6 publications

References 19 publications

The Quest for an Efficacious Antiviral for Respiratory Syncytial Virus

The Quest for an Efficacious Antiviral for Respiratory Syncytial Virus

Conformational analysis of 3′‐fluorinated A(2′‐5′)A(2′‐5′)A fragments

The solid-phase synthesis of 2-5-linked oligoriboadenylates containing 8-bromoadenine

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