Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Putting the Brakes on Drug-Resistant HIV

17.09.2010
Probing Multidrug Resistance and Protein--Ligand Interactions with Oxatricyclic Designed Ligands in HIV-1 Protease Inhibitors

HIV-1 protease inhibitors were added as a component of highly active antiretroviral therapy (HAART) in the mid-1990s, and have played a key role in that treatment regimen ever since.

However, the emergence of multidrug-resistant HIV strains requires the discovery and design of conceptually new therapeutics for the treatment of patients infected with multidrug-resistant HIV strains. In addressing this issue, the research group of Arun K. Ghosh at Purdue University developed stereochemically defined, fused tetrahydrofuran (THF) ligands based on the X-ray crystal structures of HIV--ligand complexes. The results of this project, carried out with collaborators at Georgia State University, Kumamoto University in Japan, and the National Cancer Institute, are reported in the journal ChemMedChem.

The fused THF ligands contain five contiguous chiral centers, and were synthesized in optically active form by enzymatic resolution, radical cyclization, and stereoselective reduction as key steps. The resulting HIV-1 protease inhibitors are designed to interact specifically with protein backbone atoms by hydrogen bond formation and by filling the hydrophobic active site pocket. One compound in particular, GRL-0519A, shows remarkable protease inhibition and antiviral activity. Moreover, this compound is extremely potent against various multidrug-resistant HIV-1 variants, with IC50 values ranging from 0.6 to 4.3 nanomolar. In fact, GRL-0519A is at least 10-fold better than darunavir, an FDA-approved HIV protease inhibitor that emerged from previous research by Ghosh's group.

Author: Arun K. Ghosh, Purdue University, West Lafayette, IN (USA), http://www.chem.purdue.edu/ghosh/

Title: Probing Multidrug-Resistance and Protein–Ligand Interactions with Oxatricyclic Designed Ligands in HIV-1 Protease Inhibitors

ChemMedChem, Permalink to the article: http://dx.doi.org/10.1002/cmdc.201000318

Arun K. Ghosh | ChemMedChem
Further information:
http://www.chem.purdue.edu/ghosh/
http://pressroom.chempubsoc.eu
http://dx.doi.org/10.1002/cmdc.201000318

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>