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 MicroRNA helps cancer evade immune system
19.09.2017 | Salk Institute

nachricht Ruby: Jacobs University scientists are collaborating in the development of a new type of chocolate
18.09.2017 | Jacobs University Bremen gGmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

Im Focus: Artificial Enzymes for Hydrogen Conversion

Scientists from the MPI for Chemical Energy Conversion report in the first issue of the new journal JOULE.

Cell Press has just released the first issue of Joule, a new journal dedicated to sustainable energy research. In this issue James Birrell, Olaf Rüdiger,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

New quantum phenomena in graphene superlattices

19.09.2017 | Physics and Astronomy

A simple additive to improve film quality

19.09.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>