Unpicking HIV’s invisibility cloak

February 10, 2012
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). Credit: 2012 Yu Nakagawa

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. 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 A.

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 .

Explore further: Sperm may play leading role in spreading HIV

More information: Nakagawa, Y., et al. Mapping of the primary mannose binding site of pradimicin A. Journal of the American Chemical Society 133, 17485–17493 (2011).

Related Stories

Sperm may play leading role in spreading HIV

October 26, 2009

Sperm, and not just the fluid it bathes in, can transmit HIV to macrophages, T cells, and dendritic cells (DCs), report a team led by Ana Ceballos at the University of Buenos Aires in Argentina. By infecting DCs, which carry ...

Quantum error correction in solid state processing

November 16, 2011

(PhysOrg.com) -- "Liquid state Nuclear Magnetic Resonance (NMR) has been successful for quantum information processing,” Osama Moussa tells PhysOrg.com. “However, there are some questions about scalability and other ...

Research finds HIV-killing compound

November 24, 2011

(Medical Xpress) -- A powerful topical preventative for HIV, the virus that causes AIDS, could soon be in the works thanks to a newly discovered molecular compound that research at Texas A&M University and the Scripps Research ...

Recommended for you

Isolation of Fe(IV) decamethylferrocene salts

August 29, 2016

(Phys.org)—Ferrocene is the model compound that students often learn when they are introduced to organometallic chemistry. It has an iron center that is coordinated to the π electrons in two cyclopentadienyl rings. (C5H5- ...

Bringing artificial enzymes closer to nature

August 29, 2016

Scientists at the University of Basel, ETH Zurich, and NCCR Molecular Systems Engineering have developed an artificial metalloenzyme that catalyses a reaction inside of cells without equivalent in nature. This could be a ...

New method developed for producing some metals

August 25, 2016

The MIT researchers were trying to develop a new battery, but it didn't work out that way. Instead, thanks to an unexpected finding in their lab tests, what they discovered was a whole new way of producing the metal antimony—and ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.