Polyadenylic·polyxanthylic·polyuridylic acid triple helix

Torrence, Paul F.; Clercq, Erik De

doi:10.1021/bi00625a002

Cited by 10 publications

(5 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(C),, resulting in the forniation of a product, (I),, that was inactive in inducing interferon but still capable of constituting an active interferon-inducing complex with (C),. The data further indicate that under our experimental conditions (Table 1) [4], and, as a consequence, (I), . (br5C), and (I), .…”

Section: Interferon-inducing Activitysupporting

confidence: 82%

Degradation of Poly(inosinic acid) · poly(cytidylic acid) [(I)_n· (C_n)] by Human Plasma

Clercq

1979

European Journal of Biochemistry

View full text Add to dashboard Cite

The double‐helical RNA interferon inducer, poly(inosinic acid) · poly(cytidylic acid) [(I)n· (C)n], is rapidly degraded by nucleases present in human plasma (serum). When incubated at 37°C with 50% human plasma, (I)n· (C)n (10 μg/ml) showed a half‐life of 6 min, [as assessed by residual acid insoluble radioactivity of an (I)n· (C)n preparation which was 3H‐labelled in the (C)n component]. Sucrose velocity analysis revealed that human plasma nucleases specifically hydrolyzed the (C)n strand of (I)n· (C)n, as assessed with (I)n· (C)n preparations that were 3H‐labelled in either (I)n or (C)n. The plasma nucleases that were responsible for the degradation of (I)n· (C)n resembled pancreatic ribonuclease A rather than T1 ribonuclease in substrate specificity. (I)n· (C)n became completely inactive as an inerferon inducer when it was incubated with 50% human plasma or serum. However, its interferon‐inducing capacity was fully restored if (C)n but not (I)n was added to the host cells, after these had been exposed to the inactivated (I)n· (C)n. That the inactivating effect of human plasma on the interferon‐inducing potency of (I)n· (C)n could solely be attributed to hydrolysis of the (C)n strand was further supported by the finding that two analogues of (I)n· (C)n, which had become more resistant to degradation by pancreatic ribonuclease by virtue of some substitutions in the (C)n strand, i.e. a bromine at C‐5, (I)n· (br5C)n, or a sulfur at C‐2, (I)n· (s2C)n, were not inactivated in the presence of 50% human plasma (or serum).

show abstract

Section: Interferon-inducing Activitysupporting

confidence: 82%

Degradation of Poly(inosinic acid) · poly(cytidylic acid) [(I)_n· (C_n)] by Human Plasma

Clercq

1979

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…A comparison of this correlation (Circular dichroism studies of base-modified polynucleotide duplexes have shown that alterations in the helicity of the duplex are accompanied by changes in interferon-inducing activity (Bobst et al, 1976). The concept that the induction of interferon by duplexes strongly depends on the recognition of their topology (De Clercq et al, 1974;Torrence et al, 1975; Torrence & De Clercq, 1977) was reinforced by results…”

mentioning

confidence: 98%

Interferon induction by poly(inosinic acid).cntdot.poly(cytidylic acid) segmented by spin-labels

Bobst¹,

Langemeier²,

Torrence³

et al. 1981

Biochemistry

Self Cite

View full text Add to dashboard Cite

Poly(inosinic acid).poly(cytidylic acid) [(I)n.(C)n] duplexes of which the (C)n strand was modified to various degrees chemically or enzymatically with nitroxide radicals (spin-labels) were evaluated for interferon-inducing activity. Upon annealing of the chemically modified (C)n, (1C,Cx)n (X = 1000 or 16), with (I)n, the interferon-inducing activity was similar to that of (I)n.(C)n in PRK cell cultures. However, to overcome hydrolysis of the spin-label linkage in (1C,Cx)n, and enzymatic approach was taken to synthesize (1S(4)U,Cx)n copolymers with x = 100, 38, 16, and 8. The (1s(4)U,Cx)n copolymers were chemically stable, and upon annealing with (I)n the correlation time of the nitroxide moiety in (I)n. (1s(4)U,Cx)n was determined. A comparison of this correlation time with that measured for (RUGT,U100)n.(A)n, which contains the nitroxide moiety in position 5 of the U moiety, suggests that the 1s(4)U residue is in a nonintrahelical conformation and partitions the duplex into double-helical segments of varying size. The interferon-inducing activity of (I)n. (1s(4)U,Cx)n was evaluated in primary rabbit kidney, human skin fibroblast (strain VGS), and mouse L-929 cell cultures as well as in rabbits. The 1s(4)U residue did not cause a significant change in the interferon induction as compared to (I)n.(C)n in most systems tested unless x less than 16. These findings indicate that double-helical segments of approximately 16 base pairs partitioned by nonintrahelical 1s(4)U residues suffice to trigger the interferon response in all systems studied.

show abstract

“…In the present study, we investigated the activation of (2'-5')An polymerase and protein kinase by a variety of natural and synthetic polynucleotides that have all been the subject of interferon induction studies in the past (11,16,(20)(21)(22)(23)(29)(30)(31). Table 1 shows that the two natural dsRNAs were excellent activators of both polymerase and kinase.…”

Section: Resultsmentioning

confidence: 99%

“…An polymerase or protein kinase, a large variety of polynucleotides, which have all been the subject of extensive interferon induction studies in the past, were evaluated for their abilities to activate (2'-5')A polymerase and/ or protein kinase. According to their activating effects on (2'-5')A polymerase and protein kinase (Table 1) and their interferon-inducing properties (11,16,(20)(21)(22)(23)(29)(30)(31), the polynucleotides could be grouped in five classes ( Table 2). Class I would comprise those polynucleotides that are effective inducers of interferon, and, concomitantly, potent activators of either (2'-5')An polymerase or protein kinase.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Structural requirements of polynucleotides for the activation of (2′-5′)A_npolymerase and protein kinase

1981

View full text Add to dashboard Cite

Two enzymatic pathways are involved in the inhibitory effects of double-stranded (ds)RNA on protein synthesis in cell extracts derived from interferon-treated human fibroblasts or HeLa cells, an oligonucleotide polymerase that synthesizes (2'-5')An from ATP and a protein kinase that phosphorylates the alpha subunit of initiation factor eIF-2 as well as a polypeptide of Mr = 72,000. We have now evaluated the activation of both the (2'-5')An polymerase and protein kinase by a large variety of polynucleotides, triple-stranded and synthetic dsRNAs, homopolymers, alternating copolymers, triple-stranded polymers, purine-purine duplexes and purine-pyrimidine duplexes with modifications at either the pyrimidine or ribose moieties. All these polynucleotides have been the subject of previous interferon induction studies. Some polynucleotides, i.e. (I)n.(C)n and mycophage dsRNA, which have been recognized as excellent interferon inducers, were also potent activators of both (2'-5')An polymerase and protein kinase, whereas non-inducers such as (A)n. (X)n and (A)n. (br5U)n did not activate either the kinase or the polymerase. However, some polymers like (I)n.(br5C)n, (difl)n(C)n and (dIcl)n (C)n, while potent interferon inducers and kinase activators, behaved poorly as activators of the (2'-5')An polymerase. Other polymers, i.e. (dAfl)n (U)n and (A)n.(U)nl (I)n, that do not induce interferon, activated the kinase but not the polymerase. Finally, (I)n (s2c)n, a relatively potent interferon inducer, did not activate either kinase or polymerase. These findings indicate that there is no simple relationship between the interferon-inducing ability of dsRNAs and their stimulating effects on (2'-5')An polymerase and protein kinase activity.

show abstract

Polyadenylic·polyxanthylic·polyuridylic acid triple helix

Cited by 10 publications

References 11 publications

Degradation of Poly(inosinic acid) · poly(cytidylic acid) [(I)_n· (C_n)] by Human Plasma

Degradation of Poly(inosinic acid) · poly(cytidylic acid) [(I)_n· (C_n)] by Human Plasma

Interferon induction by poly(inosinic acid).cntdot.poly(cytidylic acid) segmented by spin-labels

Structural requirements of polynucleotides for the activation of (2′-5′)A_npolymerase and protein kinase

Contact Info

Product

Resources

About

Polyadenylic·polyxanthylic·polyuridylic acid triple helix

Cited by 10 publications

References 11 publications

Degradation of Poly(inosinic acid) · poly(cytidylic acid) [(I)n· (Cn)] by Human Plasma

Degradation of Poly(inosinic acid) · poly(cytidylic acid) [(I)n· (Cn)] by Human Plasma

Interferon induction by poly(inosinic acid).cntdot.poly(cytidylic acid) segmented by spin-labels

Structural requirements of polynucleotides for the activation of (2′-5′)Anpolymerase and protein kinase

Contact Info

Product

Resources

About

Degradation of Poly(inosinic acid) · poly(cytidylic acid) [(I)_n· (C_n)] by Human Plasma

Degradation of Poly(inosinic acid) · poly(cytidylic acid) [(I)_n· (C_n)] by Human Plasma

Structural requirements of polynucleotides for the activation of (2′-5′)A_npolymerase and protein kinase