Abstract
Poly (2-azaadenylic acid) [(aza2A)n] and poly(2-azainosinic acid [(aza2I)n], two newly synthesized analogues of (A)n and (I)n, in which CH-2 of the purine ring is replaced by a nitrogen atom, have been evaluated in various biological assay systems. (Aza2A) n formed a complex with (U)n and (br5U)n, and (aza2I)n formed a complex with (C)n and (br5C)n, but these complexes were markedly destabilized relative to the corresponding (A)n or (I)n complexes. The (aza2A)n-and (aza2I)n-derived complexes failed to stimulate the production of interferon in primary rabbit kidney cells and human diploid fibroblasts, under conditions (A)n. (U)n, (I)n. (C)n and (I)n. (br5C)n induced high amounts of interferon. both (aza2A)n and (aza2I)n exerted a marked inhibitory effect on the endogenous RNA directed DNA polymerase (reverse transcriptase) activity associated with murine leukemia virus. They caused a relatively mild inhibition of complement activity in an hemolytic assay system.
Full text
PDF










Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arya S. K., Carter W. A., Alderfer J. L., Ts'o P. O. Inhibition of RNA directed DNA polymerase of murine leukemia virus by 2'-O-alkylated polyadenylic acids. Biochem Biophys Res Commun. 1974 Jul 24;59(2):608–615. doi: 10.1016/s0006-291x(74)80023-9. [DOI] [PubMed] [Google Scholar]
- Arya S. K., Helser T. L., Carter W. A. Polyxanthylic and polyguanylic acid inhibition of murine leukemia virus activities. Mol Pharmacol. 1976 Sep;12(5):844–853. [PubMed] [Google Scholar]
- Clercq E. D., Edy V. G., Torrence P. F., Waters J. A., Witkop B. Antiviral activity of poly(7-deazainosinic acid)-derived complexes in vitro and in vivo. Mol Pharmacol. 1976 Nov;12(6):1045–1051. [PubMed] [Google Scholar]
- De Clercq E., Billiau A., Hattori M., Ikehara M. Inhibition of oncornavirus functions by poly (2-methylthioinosinic acid). Nucleic Acids Res. 1975 Dec;2(12):2305–2313. doi: 10.1093/nar/2.12.2305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Clercq E., Billiau A., Hobbs J., Torrence P. F., Witkop B. Inhibition of oncornavirus functions by 2'-azido polynucleotides. Proc Natl Acad Sci U S A. 1975 Jan;72(1):284–288. doi: 10.1073/pnas.72.1.284. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Clercq E., Torrence P. F., De Somer P., Witkop B. Biological, biochemical, and physicochemical evidence for the existence of the polyadenylic-polyuridylic-polyinosinic acid triplex. J Biol Chem. 1975 Apr 10;250(7):2521–2531. [PubMed] [Google Scholar]
- De Clercq E., Torrence P. F., Hobbs J., Janik B., De Somer P., Witkop B. Anti-complement activity of polynucleotides. Biochem Biophys Res Commun. 1975 Nov 3;67(1):255–263. doi: 10.1016/0006-291x(75)90310-1. [DOI] [PubMed] [Google Scholar]
- De Clercq E., Torrence P. F., Witkop B. Interferon induction by synthetic polynucleotides: importance of purine N-7 and strandwise rearrangement. Proc Natl Acad Sci U S A. 1974 Jan;71(1):182–186. doi: 10.1073/pnas.71.1.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Clercq E., Torrence P. F., Witkop B. Polynucleotide displacement reactions: detection by interferon induction. Biochemistry. 1976 Feb 24;15(4):717–724. doi: 10.1021/bi00649a001. [DOI] [PubMed] [Google Scholar]
- Johnston M. D., Atherton K. T., Hutchinson D. W., Burke D. C. The binding of poly(rI) - poly(rC) to human fibroblasts and the induction of interferon. Biochim Biophys Acta. 1976 Jun 2;435(1):69–75. doi: 10.1016/0005-2787(76)90192-1. [DOI] [PubMed] [Google Scholar]
- Kawana M., Ivanovics G. A., Rousseau R. J., Robins R. K. Azapurine nucleosides. 3. Synthesis of 7-( -D-ribofuranosyl)imidazo(4,5-d)-v-triazin-4-one(2-azainosine) and related derivatives. J Med Chem. 1972 Aug;15(8):841–843. doi: 10.1021/jm00278a012. [DOI] [PubMed] [Google Scholar]
- Torrence P. F., Bobst A. M., Waters J. A., Witkop B. Synthesis and characterization of potential interferon inducers. Poly(2'-azido-2'-deoxyuridylic acid). Biochemistry. 1973 Sep 25;12(20):3962–3972. doi: 10.1021/bi00744a028. [DOI] [PubMed] [Google Scholar]
- Torrence P. F., De Clercq E., Waters J. A., Witkop B. A potent interferon inducer derived from poly (7-deazainosinic acid). Biochemistry. 1974 Oct 8;13(21):4400–4408. doi: 10.1021/bi00718a025. [DOI] [PubMed] [Google Scholar]
- Torrence P. F., De Clercq E., Waters J. A., Witkop B. Failure of duplexes based on polylaurusin (poly(L), "Polyformycin B") to induce interferon. Biochem Biophys Res Commun. 1975 Feb 3;62(3):658–664. doi: 10.1016/0006-291x(75)90449-0. [DOI] [PubMed] [Google Scholar]
- Torrence P. F., De Clercq E., Witkop B. Triple-helical polynucleotides. Mixed triplexes of the poly(uridylic acid)-poly(adenylic acid)-poly(uridylic acid) class. Biochemistry. 1976 Feb 24;15(4):724–734. doi: 10.1021/bi00649a002. [DOI] [PubMed] [Google Scholar]
- de Clercq E., Billiau A., Torrence P. F., Waters J. A., Witkop B. Antiviral and antimetabolic activities of poly (7-deazaadenylic acid) and poly (7-deazainosinic acid). Biochem Pharmacol. 1975 Dec 15;24(24):2233–2238. doi: 10.1016/0006-2952(75)90260-9. [DOI] [PubMed] [Google Scholar]
- de Clercq E., Torrence P. F., Fukui T., Ikehara M. Role of purine N-3 in the biologic activities of poly(A) and poly(I). Nucleic Acids Res. 1976 Jun;3(6):1591–1601. doi: 10.1093/nar/3.6.1591. [DOI] [PMC free article] [PubMed] [Google Scholar]
