These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Inhibition of DNA topoisomerase I activity by 2',5'-oligoadenylates and mismatched double-stranded RNA in uninfected and HIV-1-infected H9 cells.
    Author: Schröder HC, Kelve M, Schäcke H, Pfleiderer W, Charubala R, Suhadolnik RJ, Müller WE.
    Journal: Chem Biol Interact; 1994 Feb; 90(2):169-83. PubMed ID: 8156606.
    Abstract:
    2',5'-Oligoadenylates (2-5As) inhibit the type I DNA topoisomerase activity both in uninfected and HIV-1-infected human T cell line H9 as well as the purified enzyme (calf thymus). Topoisomerase I activity was determined by measuring the relaxation of negatively supercoiled pBR322 DNA. Inhibition of topoisomerase I by 2-5A depends on the chain length of the oligomer and the presence of 5'-phosphate. The 5'-triphosphate of the 2-5A hexamer was most active (almost total inhibition of DNA relaxation at 10 microM concentration); the 2-5A core trimer (at 100 microM) displayed no significant effect. In crosslinking and immunoprecipitation experiments we present evidence that 2-5A (32P-labelled 2-5A derivative, ppp(A2'p)3 A[32P]pCp) is able to bind to nuclear topoisomerase I. The mismatched dsRNA, poly(I).poly(C12U) (Ampligen), exhibited a strong anti-HIV-1 activity. However, our data show that this antiviral effect is not related to topoisomerase I inhibition. On the other hand, we did observe the production of longer oligomers of 2-5A in cells treated with poly(I).poly(C12U). It remains speculative, whether the in vivo effect could be catalyzed by this activity of poly(I).poly(C12U). In addition we could show that 2-5A also inhibits topoisomerase I activity associated with isolated HIV-1 particles.
    [Abstract] [Full Text] [Related] [New Search]