Journal home
Advance online publication
Current issue
Archive
Press releases
Supplements
Focuses
Guide to authors
Online submissionOnline submission
For referees
Free online issue
Contact the journal
Subscribe
Advertising
work@npg
Reprints and permissions
About this site
For librarians
 
NPG Resources
Nature
Nature Reviews
Nature Immunology
Nature Cell Biology
Nature Genetics
news@nature.com
Nature Conferences
Dissect Medicine
NPG Subject areas
Biotechnology
Cancer
Chemistry
Clinical Medicine
Dentistry
Development
Drug Discovery
Earth Sciences
Evolution & Ecology
Genetics
Immunology
Materials Science
Medical Research
Microbiology
Molecular Cell Biology
Neuroscience
Pharmacology
Physics
Browse all publications
News and Views
Nature Medicine  1, 519 - 520 (1995)
doi:10.1038/nm0695-519

Rational drug design and HIV: Hopes and limitations

Roger S. Goody

Max-Planck-Institut für, Molekulare Physiologie, 44026 Dortmund, Germany

Despite its early promise, rational drug design for anti-HIV agents has fallen short of expectations, probably because the expectations were too high.

REFERENCES
  1. Abdel-Meguid, S.S. Inhibitors of aspartyl proteinases. Med. Res. Rev. 13, 731−778 (1993). | PubMed  | ChemPort |
  2. Pauwels, R. et al. Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives. Nature 343, 470−474 (1990). | Article | PubMed  | ISI | ChemPort |
  3. Kohlstaedt, L.A., Wang, J., Friedman, J.M., Rice, P.A. & Steitz, T.A. Crystal structure at 3.5 Å resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256, 1783−1790 (1992). | PubMed  | ISI | ChemPort |
  4. Jacobo-Molina, A. et al. Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 Å resolution shows bent DNA. Proc. natn. Acad. Sci. U.S.A. 90, 6320−6324 (1993). | ChemPort |
  5. Smerdon, S.J. et al. Structure of the binding site for nonnucleoside inhibitors of the reverse transcriptase of human immunodeficiency virus type 1. Proc. natn. Acad. Sci. U.S.A. 91, 3911−3915 (1994). | ChemPort |
  6. Ding, J. et al. Structure of HIV-1 reverse transcriptase in a complex with the non-nucleoside inhibitor alpha-APA R 95845 at 2.8 Å resolution. Structure 3 365−379 (1995). | PubMed  | ISI | ChemPort |
  7. Ren, J.S. et al. High resolution structure of HIV-1 RT: Insights from four RT-inhibitor complexes. Nature struct. Biol. 2 293−302 (1995). | PubMed  | ISI | ChemPort |
  8. Esnouf, R. et al. Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside inhibitors. Nature struct. Biol. 2 303−308 (1995). | PubMed  | ISI | ChemPort |
  9. Rodgers, D.W. et al. The structure of unliganded reverse transcriptase from the human immunodeficiency virus type 1. Proc. natn. Acad. Sci. U.S.A. 92 1222−1226 (1995). | ChemPort |
  10. Spence, R.A., Kati, W.M., Anderson, K.S. & Johnson, K.A. Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors. Science 267 988−993 (1995). | PubMed  | ISI | ChemPort |
  11. Rittinger, K., Divita, G., Muller, B. & Goody, R.S. HIV reverse transcriptase substrate-induced conformational changes and the mechanism of inhibition by non-nucleoside inhibitors. Proc. natn. Acad. Sci. U.S.A. (in the press).
  12. Collins, J.R., Burt, S.K. & Erickson, J.W. Flap opening in HIV-1 protease simulated by 'activated' molecular dynamics. Nature struct. Biol. 2 334−338 (1995). | PubMed  | ISI | ChemPort |
  13. Caspar, D. Problems in simulating macromolecular movements. Structure 3 327−329 (1995). | PubMed  | ISI | ChemPort |
  14. Condra, J.H. et al. In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature 374, 569−571 (1995). | Article | PubMed  | ISI | ChemPort |
  15. Tisdale, M., Kemp, S.D., Parry, N.R. & Larder, B.A. Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. Proc. natn. Acad. Sci. U.S.A. 90, 5653−5656 (1993). | ChemPort |
  16. Divita, G., Restle, T., Goody, R.S., Chermann, J.-C. & Baillon, J.G. Inhibition of human immunodeficiency virus type I reverse transcriptase dimerization using synthetic peptides derived from the connection domain. J. biol. Chem. 269, 13080−13083 (1994). | PubMed  | ISI | ChemPort |
  17. Liuzzi, M. et al. A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo. Nature 372, 695−698 (1994). | Article | PubMed  | ISI | ChemPort |
  18. Bushman, F. Targeting retroviral integration. Science 267 1443−1444 (1995) | PubMed  | ISI | ChemPort |
  19. Lasic, D.D. & Papahadjopulos, D. Liposomes revisited. Science 267 1275−1276 (1995). | PubMed  | ISI | ChemPort |
 Top
 Top
References
Previous | Next
Table of contents
Download PDFDownload PDF
Send to a friendSend to a friend
Save this linkSave this link
References
Export citation
Export references
natureproducts

Search buyers guide:

 
ADVERTISEMENT
 
Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
Journal home | Advance online publication | Current issue | Archive | Press releases | Supplements | Focuses | For authors | Online submission | For referees | Free online issue | About the journal | Contact the journal | Subscribe | Advertising | work@npg | Reprints and permissions | About this site | For librarians
Nature Publishing Group, publisher of Nature, and other science journals and reference works©1995 Nature Publishing Group | Privacy policy