Inhibition of rous sarcoma virus production by formycin

Sarih, Leila; Agoutin, Bernadette; Lecoq, Odile; Weill, Dominique; Jullien, P.; Heyman, T.

doi:10.1016/0042-6822(85)90212-0

Cited by 4 publications

(2 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The nucleoside formycin has been shown to have numerous biological and pharmacological properties. It inhibits the production of influenza virus (Takeuchi et al, 1966), suppresses synthesis of avian myleoblastosis cDNA, and suppresses synthesis of the rous sarcoma virus (Sarih et al, 1985). It is cytotoxic in neoplasms (Hori et al, 1964; Umezawa et al, 1967), and this cytotoxicity is enhanced by the addition of 2/-deoxycoformycin (Crabtree et al, 1981; Chu et al, 1981;Spemulli et al, 1983).…”

mentioning

confidence: 99%

Crystal structure of formycin 5'-phosphate: an explanation for its tight binding to AMP nucleosidase

Giranda¹,

Berman²,

Schramm³

1988

Biochemistry

View full text Add to dashboard Cite

Formycin 5'-monophosphate (FMP) is a strong competitive inhibitor of AMP nucleosidase with Km/Kis from 1200 to 2600 depending on the source of the enzyme. The crystal structure of FMP has been determined in order to understand the basis for its high affinity for AMP nucleosidases and other biological properties. The key structural features of FMP are (1) the base is the N(7)-H tautomer, (2) the N(3) of the base forms an intramolecular hydrogen bond to the phosphate oxygen O(1), (3) the glycosyl torsion angle is syn with O(4')-C(1') relative to C(9)-C(4) being -6.43 degrees, and (4) the furanose ring pucker is C(3')-endo, with a pseudorotation angle of 20.3 degrees. The major difference between the AMP and FMP structures is that the glycosyl torsion angles differ by 190 degrees. The computed conformational energy necessary to distort AMP so that it has the same glycosyl torsion angle as FMP is 4.6 kcal/mol. This corresponds to a 2100-fold difference in binding energy, in good agreement with the observed interaction between AMP nucleosidase and FMP.

show abstract

mentioning

confidence: 99%

Crystal structure of formycin 5'-phosphate: an explanation for its tight binding to AMP nucleosidase

Giranda¹,

Berman²,

Schramm³

1988

Biochemistry

View full text Add to dashboard Cite

show abstract

“…2; There are no previous reports of antiviral activity associated with 8-azaadenosine. Formycin A derivatives have previously been noted to possess antiretroviral activity, though no detailed studies have been conducted (18,19). Our study, to the best of our knowledge, is the first to demonstrate the antiretroviral activity of formycin A.…”

Section: Discussionmentioning

confidence: 63%

Discovery of Novel Ribonucleoside Analogs with Activity against Human Immunodeficiency Virus Type 1

Dapp

Bonnac

Patterson

et al. 2014

J Virol

View full text Add to dashboard Cite

Reverse transcription is an important early step in retrovirus replication and is a key point targeted by evolutionarily conserved host restriction factors (e.g., APOBEC3G, SamHD1). Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a major target of antiretroviral drugs, and concerns regarding drug resistance and off-target effects have led to continued efforts for identifying novel approaches to targeting HIV-1 RT. Several observations, including those obtained from monocytederived macrophages, have argued that ribonucleotides and their analogs can, intriguingly, impact reverse transcription. For example, we have previously demonstrated that 5-azacytidine has its greatest antiviral potency during reverse transcription by enhancement of G-to-C transversion mutations. In the study described here, we investigated a panel of ribonucleoside analogs for their ability to affect HIV-1 replication during the reverse transcription process. We discovered five ribonucleosides-8-azaadenosine, formycin A, 3-deazauridine, 5-fluorocytidine, and 2=-C-methylcytidine-that possess anti-HIV-1 activity, and one of these (i.e., 3-deazauridine) has a primary antiviral mechanism that involves increased HIV-1 mutational loads, while quantitative PCR analysis determined that the others resulted in premature chain termination. Taken together, our findings provide the first demonstration of a series of ribonucleoside analogs that can target HIV-1 reverse transcription with primary antiretroviral mechanisms that include premature termination of viral DNA synthesis or enhanced viral mutagenesis.

show abstract

Formycins and their Analogues: Purine Nucleoside Phosphorylase Inhibitors and their Potential Application in Immunosuppression and Cancer

Bzowska

2008

Modified Nucleosides

View full text Add to dashboard Cite

Inhibition of rous sarcoma virus production by formycin

Cited by 4 publications

References 11 publications

Crystal structure of formycin 5'-phosphate: an explanation for its tight binding to AMP nucleosidase

Crystal structure of formycin 5'-phosphate: an explanation for its tight binding to AMP nucleosidase

Discovery of Novel Ribonucleoside Analogs with Activity against Human Immunodeficiency Virus Type 1

Formycins and their Analogues: Purine Nucleoside Phosphorylase Inhibitors and their Potential Application in Immunosuppression and Cancer

Contact Info

Product

Resources

About