Search

Your search keyword '"de Bethune, Marie-Pierre"' showing total 20 results
Start Over Author "de Bethune, Marie-Pierre"
20 results on '"de Bethune, Marie-Pierre"'

5. Modulation of human immunodeficiency virus type I synergistic inhibition by reverse transcriptase mutations

Author

Basavapathruni, Aravind, Vingerhoets, Johan, De Bethune, Marie-Pierre, Chung, Raymond, Bailey, Christopher M., Kim, Jiae, and Anderson, Karen S.

Subjects
HIV (Viruses) -- Genetic aspects, Nucleosides -- Chemical properties, Nucleosides -- Structure, Reverse transcriptase -- Chemical properties, Gene mutations -- Research, Biological sciences, Chemistry
Abstract

Modulation of human immunodeficiency virus type I synergistic inhibition by reverse transcriptase (RT) mechanism was examined. The synergy between the anti-human immunodeficiency virus type I (HIV) nucleoside RT inhibitors (NRTIs) and nonnucloside RT inhibitors (NNRTIs) results from a general mechanism in which NNRTIs inhibit ATP-mediated removal of NRTIs from chain-terminated primers. This requires NNRTIs that are potent against wild type virus and possess favorable activity profiles against clinically relevant mutations.

Published
2006

8. Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 gag-pol

Author

Figueiredo, Anna, Moore, Katie L., Mak, Johnson, Sluis-Cremer, Nicolas, de Bethune, Marie-Pierre, Tachedjian, Gilda, Figueiredo, Anna, Moore, Katie L., Mak, Johnson, Sluis-Cremer, Nicolas, de Bethune, Marie-Pierre, and Tachedjian, Gilda

Abstract

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) target HIV-1 reverse transcriptase (RT) by binding to a pocket in RT that is close to, but distinct, from the DNA polymerase active site and prevent the synthesis of viral cDNA. NNRTIs, in particular, those that are potent inhibitors of RT polymerase activity, can also act as chemical enhancers of the enzyme's inter-subunit interactions. However, the consequences of this chemical enhancement effect on HIV-1 replication are not understood. Here, we show that the potent NNRTIs efavirenz, TMC120, and TMC125, but not nevirapine or delavirdine, inhibit the late stages of HIV-1 replication. These potent NNRTIs enhanced the intracellular processing of Gag and Gag-Pol polyproteins, and this was associated with a decrease in viral particle production from HIV-1-transfected cells. The increased polyprotein processing is consistent with premature activation of the HIV-1 protease by NNRTI-enhanced Gag-Pol multimerization through the embedded RT sequence. These findings support the view that Gag-Pol multimerization is an important step in viral assembly and demonstrate that regulation of Gag-Pol/Gag-Pol interactions is a novel target for small molecule inhibitors of HIV-1 production. Furthermore, these drugs can serve as useful probes to further understand processes involved in HIV-1 particle assembly and maturation.

Published
2006

10. Design of HIV-1 Protease Inhibitors Active on Multidrug-Resistant Virus

Author

Surleraux, Dominique L. N. G., primary, de Kock, Herman A., additional, Verschueren, Wim G., additional, Pille, Geert M. E., additional, Maes, Louis J. R., additional, Peeters, Anik, additional, Vendeville, Sandrine, additional, De Meyer, Sandra, additional, Azijn, Hilde, additional, Pauwels, Rudi, additional, de Bethune, Marie-Pierre, additional, King, Nancy M., additional, Prabu-Jeyabalan, Moses, additional, Schiffer, Celia A., additional, and Wigerinck, Piet B. T. P., additional

Published
2005
Full Text
View/download PDF

11. Discovery and Selection of TMC114, a Next Generation HIV-1 Protease Inhibitor

Author

Surleraux, Dominique L. N. G., primary, Tahri, Abdellah, additional, Verschueren, Wim G., additional, Pille, Geert M. E., additional, de Kock, Herman A., additional, Jonckers, Tim H. M., additional, Peeters, Anik, additional, De Meyer, Sandra, additional, Azijn, Hilde, additional, Pauwels, Rudi, additional, de Bethune, Marie-Pierre, additional, King, Nancy M., additional, Prabu-Jeyabalan, Moses, additional, Schiffer, Celia A., additional, and Wigerinck, Piet B. T. P., additional

Published
2004
Full Text
View/download PDF

13. Evolution of anti-HIV drug candidates. Part 3: diarylpyrimidine (DAPY) analogues

Author

Ludovici, Donald W., De Corte, Bart L., Kukla, Michael J., Ye, Hong, Ho, Chih Y., Lichtenstein, Mark A., Kavash, Robert W., Andries, Koen, de Béthune, Marie-Pierre, Azijn, Hilde, Pauwels, Rudi, Lewi, Paul J., Heeres, Jan, Koymans, Lucien M.H., de Jonge, Marc R., Van Aken, Koen J.A., Daeyaert, Frederik F.D., Das, Kalyan, Arnold, Edward, and Janssen, Paul A.J.

Published
2001
Full Text
View/download PDF

15. Evolution of Anti-HIV Drug CandidatesPart 2: Diaryltriazine (DATA) Analogues

Author

Ludovici, Donald W., Kavash, Robert W., Kukla, Michael J., Ho, Chih Y., Ye, Hong, De Corte, Bart L., Andries, Koen, de Béthune, Marie-Pierre, Azijn, Hilde, Pauwels, Rudi, Moereels, Henry E.L., Heeres, Jan, Koymans, Lucien M.H., de Jonge, Marc R., Van Aken, Koen J.A., Daeyaert, Frederik F.D., J. Lewi, Paul, Das, Kalyan, Arnold, Edward, and Janssen, Paul A.J.

Published
2001
Full Text
View/download PDF

16. Characterisation of the Binding of Virginiamycin S to <em>Escherichia coli</em> Ribosomes.

Author

de Bethune, Marie-Pierre and Nierhaus, Knud H.

Subjects
*ESCHERICHIA coli, *RIBOSOMES, *BIOCHEMISTRY, *BACTERIOLOGY, *MOLECULAR microbiology, *MOLECULAR biology, *BIOLOGY
Abstract

Virginiamycin S is an inhibitor of protein synthesis in vivo. In this paper we show by equilibrium dialysis that it binds specifically to the 50-S subunit of Escherichia coli ribosomes, with one binding site per subunit. This binding is not altered by the presence of chloramphenicol, tetracycline or puromycin but is competed for by erythromycin. Using the splitting-reconstitution method, it could be demonstrated that protein L16 is absolutely required for the binding of virginiamycin S to the 50-S subunit. [ABSTRACT FROM AUTHOR]

Published
1978
Full Text
View/download PDF

20. Discovery and selection of TMC114, a next generation HIV-1 protease inhibitor.

Author

Surleraux DL, Tahri A, Verschueren WG, Pille GM, de Kock HA, Jonckers TH, Peeters A, De Meyer S, Azijn H, Pauwels R, de Bethune MP, King NM, Prabu-Jeyabalan M, Schiffer CA, and Wigerinck PB

Subjects
Administration, Oral, Animals, Biological Availability, Cell Line, Crystallography, X-Ray, Darunavir, Dogs, Drug Resistance, Multiple, Viral, HIV Protease genetics, HIV Protease Inhibitors pharmacokinetics, HIV Protease Inhibitors pharmacology, HIV-1 genetics, Humans, In Vitro Techniques, Microsomes, Liver metabolism, Models, Molecular, Molecular Conformation, Mutation, Rats, Stereoisomerism, Structure-Activity Relationship, Sulfonamides pharmacokinetics, Sulfonamides pharmacology, Thermodynamics, HIV Protease metabolism, HIV Protease Inhibitors chemical synthesis, HIV-1 drug effects, Sulfonamides chemical synthesis
Abstract

The screening of known HIV-1 protease inhibitors against a panel of multi-drug-resistant viruses revealed the potent activity of TMC126 on drug-resistant mutants. In comparison to amprenavir, the improved affinity of TMC126 is largely the result of one extra hydrogen bond to the backbone of the protein in the P2 pocket. Modification of the substitution pattern on the phenylsulfonamide P2' substituent of TMC126 created an interesting SAR, with the close analogue TMC114 being found to have a similar antiviral activity against the mutant and the wild-type viruses. X-ray and thermodynamic studies on both wild-type and mutant enzymes showed an extremely high enthalpy driven affinity of TMC114 for HIV-1 protease. In vitro selection of mutants resistant to TMC114 starting from wild-type virus proved to be extremely difficult; this was not the case for other close analogues. Therefore, the extra H-bond to the backbone in the P2 pocket cannot be the only explanation for the interesting antiviral profile of TMC114. Absorption studies in animals indicated that TMC114 has pharmacokinetic properties comparable to currently approved HIV-1 protease inhibitors.

Published
2005
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results