de.mpg.escidoc.pubman.appbase.FacesBean
English
 
Help Guide Disclaimer Contact us Login
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Synthesis of 21,31,51-trideoxyuridine-51-methylphosphonic acid and its diphosphate derivative. Study of the interaction with HIV-1reverse transcriptase

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons94973

Rittinger,  Katrin
Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons196902

Divita,  Gilles
Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons93142

Goody,  R.S
Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

Fulltext (public)
There are no public fulltexts available
Supplementary Material (public)
There is no public supplementary material available
Citation

Benzaria, S., Maury, G., Gosselin, G., Rittinger, K., Divita, G., Goody, R., et al. (1994). Synthesis of 21,31,51-trideoxyuridine-51-methylphosphonic acid and its diphosphate derivative. Study of the interaction with HIV-1reverse transcriptase. Antiviral Chemistry & Chemotherapy, 5(4), 221-228. doi:10.1177/095632029400500403.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002A-F1D5-5
Abstract
2′,3′,5′-Trideoxyuridine-5′-methylphosphonate, [8], was synthesized from ddU. The 5′,6′ carbon-carbon bond was formed by condensing the 5′-aldehyde of ddU and a Wittig reagent. The binding interaction of the diphosphate derivative [10] of the phosphonate [8] with HIV-1 reverse transcriptase (RT) was studied using methods based primarily on fluorescence spectroscopy. From the quenching of intrinsic tryptophan fluorescence of RT during its titration against [10], a dissociation constant of 24 μm was calculated at 25°C. In the presence of a DNA/DNA template/primer of defined sequence and RT, [10] and a fluorescent derivative of ddTTP competed for binding to RT without incorporation of ddU-5′-methylphosphonate. In the presence of a 0.5 mm concentration of [10], the RT activity measured with Poly(rA)/(dT)15 and [3H] dTTP was lowered to 65%. All our observations are consistent with suppression of the catalysis of bond formation between the OH at the primer 3′-end and α-P of [10] after formation of the complex between RT, template/primer and [10].