Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Unpicking HIV’s invisibility cloak

13.02.2012
Revelation of how certain compounds adhere so strongly to HIV’s coat points to a fresh therapeutic approach

Drug researchers hunting for alternative ways to treat human immunodeficiency virus (HIV) infections may soon have a novel target—its camouflage coat. HIV hides inside a cloak unusually rich in a sugar called mannose, which it uses to slip past the immune system before infecting its host’s cells.


Figure 1: The compound pradimicin A disrupts the human immunodeficiency virus (HIV) by clinging to its mannose-rich coat. The mannose sits within a cavity in the pradimicin A structure (purple shading). Copyright : 2012 Yu Nakagawa

Recently, however, biochemists discovered a family of chemical compounds that stick strongly to mannose. Understanding how this mechanism works could reveal a way to make drugs adhere to and kill HIV. Yu Nakagawa and Yukishige Ito at the RIKEN Advanced Science Institute in Wako and their colleagues from several research institutes in Japan are leading the effort: they have mapped the binding site of the mannose-binding compound pradimicin A1.

Mannose-binding compounds are particularly attractive to drug researchers thanks to their double-action anti-HIV effect. By sticking to mannose in the virus’s coat, pradimicin A first freezes HIV’s molecular machinery for entering and infecting its host’s healthy cells. The virus responds by reducing the mannose in its coat thereby revealing itself to the immune system, which can then attack.

Unraveling just how pradimicin A recognizes mannose, however, has proven surprisingly difficult. In solution, the two components stick together in variously sized small clusters, confounding conventional analytical techniques such as solution-based nuclear magnetic resonance (NMR) and x-ray crystallography. Nakagawa, Ito and their colleagues side-stepped the clumping problem by using solid-state NMR, which allowed them analyze the compounds as solids, rather than in solution.

The research team’s approach involved inserting carbon-13, a chemical label, into particular parts of the pradimicin A structure. Carbon-13 boosts the NMR signal wherever it is inserted, so the team could ‘walk’ around the compound and detect where it interacts most strongly with mannose.

The results revealed that pradimicin A curls up to form a cavity, within which the mannose structure sits (Fig. 1). “Our study highlights the benefit of solid-state NMR methodology to investigate this interaction,” says Nakagawa. “Solid-state NMR is, at present, the only technique to analyze such a complicated system.” Flagging the potential utility of the technique, Nakagawa adds that: “Our analytical strategy might be applicable to other systems that similarly suffer from aggregation in solution.”

Meanwhile, solid-state NMR can offer even more in probing mannose–pradimicin A binding, Nakagawa says. Having determined how and where pradimicin A grabs mannose, the team’s next step will be to use the technique to identify the specific molecular interactions that bind the pradmicin A to this potential Achilles' heel of HIV.

The corresponding author for this highlight is based at the Synthetic Cellular Chemistry Laboratory, RIKEN Advanced Science Institute

gro-pr | Research asia research news
Further information:
http://www.riken.jp
http://www.researchsea.com

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>