Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Pushing the envelope to overcome HIV drug resistance

18.10.2004


The evolution of resistance to currently prescribed HIV-1 protease inhibitors is devastating to patients and is surprising given the way these drugs work. Protease inhibitors are all small-molecule, competitive, active-site inhibitors--low molecular weight compounds that fit squarely in the center of the active site of HIV-1 protease and prevent protein processing that is essential to the replication of the virus. It would seem as though mutations occurring in the protease that prevent drug binding and result in drug resistance would also prevent normal substrate binding, and thus compensatory changes in the substrate would be required for the virus to survive. However, research from the lab of Celia Schiffer at the University of Massachusetts Medical School has revealed a common structural theme in protease inhibitor resistance.



By comparing the structures of several substrate-protease complexes, they establish a "substrate envelope" to define the three-dimensional shape that is shared by all the substrates as they are bound in the active site. They then go on to define an "inhibitor envelope" that shows how numerous protease inhibitors fit only partially within the substrate envelope. Where the inhibitors protrude beyond the confines of the substrate envelope, there is the potential for unique molecular contacts to the protease. Also, when the protease mutates at unique sites that contact the inhibitor envelope but not the substrate envelope, drug resistance emerges. This general principle offers a rational basis for combating drug resistance more aggressively by preventing a common mode of escape. Such a tool would be of enormous benefit in the worldwide fight against AIDS.

Nancy M. King, Moses Prabu-Jeyabalan, Ellen A. Nalivaika, and Celia A. Schiffer: "Combating Susceptibility to Drug Resistance: Lessons from HIV-1 Protease"

Heidi Hardman | EurekAlert!
Further information:
http://www.cell.com

More articles from Health and Medicine:

nachricht Research offers clues for improved influenza vaccine design
09.04.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Injecting gene cocktail into mouse pancreas leads to humanlike tumors
06.04.2018 | University of Texas Health Science Center at San Antonio

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

Im Focus: The Future of Ultrafast Solid-State Physics

In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.

Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...

Im Focus: Stronger evidence for a weaker Atlantic overturning

The Atlantic overturning – one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards – is weaker today than any time before in more than 1000 years. Sea surface temperature data analysis provides new evidence that this major ocean circulation has slowed down by roughly 15 percent since the middle of the 20th century, according to a study published in the highly renowned journal Nature by an international team of scientists. Human-made climate change is a prime suspect for these worrying observations.

“We detected a specific pattern of ocean cooling south of Greenland and unusual warming off the US coast – which is highly characteristic for a slowdown of the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Improved stability of plastic light-emitting diodes

19.04.2018 | Power and Electrical Engineering

Enduring cold temperatures alters fat cell epigenetics

19.04.2018 | Life Sciences

New capabilities at NSLS-II set to advance materials science

18.04.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>