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Failed HIV Drug Gets Second Chance with Addition of Gold Nanoparticles
May 27, 2008Researchers at North Carolina State University have discovered that adding tiny bits of gold to a failed HIV drug rekindle the drug's ability to stop the virus from invading the body's immune system.
The addition of gold nanoparticles to a modified version of a drug designed in the 1990s to combat HIV - but discarded due to its harmful side effects - creates a compound that prevents the virus from gaining a cellular foothold, say Dr. Christian Melander, assistant professor of chemistry at NC State, and doctoral student T. Eric Ballard.
Their findings appear online in the Journal of the American Chemical Society.
The drug, a compound known as TAK-779, was originally found to bind to a specific location on human T-cells, which blocks the HIV virus' entry to the body's immune system. Unfortunately, the portion of the drug's molecule that made binding possible had unpleasant side effects. When that portion of the molecule - an ammonium salt - was removed, the drug lost its binding ability.
That's when the researchers turned to gold as the answer. The element is non-reactive in the human body, and would be the perfect "scaffold" to attach molecules of the drug to in the absence of the ammonium salt, holding the drug molecules together and concentrating their effect.
"The idea is that by attaching these individual molecules of the drug with a weak binding ability to the gold nanoparticle, you can magnify their ability to bind," Melander says.
The researchers' theory proved correct. They started with a modified version of TAK-779, which didn't include the harmful ammonium salt. After testing, they found that attaching 12 molecules of the modified drug (SDC-1721) to one nanoparticle of gold restored the drug's ability to prevent HIV infection in primary cultured patient cells. When only one molecule of the drug was attached to the gold nanoparticle, the compound was unable to prevent HIV infection, indicating that the multivalency of the drug was important for its activity.
"We've discovered a non-harmful way to improve the strength and efficacy of an important drug," Melander says. "There's no reason to think that this same process can't be used with similar effect on other existing drugs."
North Carolina State University
The drug, a compound known as TAK-779, was originally found to bind to a specific location on human T-cells, which blocks the HIV virus' entry to the body's immune system. Unfortunately, the portion of the drug's molecule that made binding possible had unpleasant side effects. When that portion of the molecule - an ammonium salt - was removed, the drug lost its binding ability.
That's when the researchers turned to gold as the answer. The element is non-reactive in the human body, and would be the perfect "scaffold" to attach molecules of the drug to in the absence of the ammonium salt, holding the drug molecules together and concentrating their effect.
"The idea is that by attaching these individual molecules of the drug with a weak binding ability to the gold nanoparticle, you can magnify their ability to bind," Melander says.
The researchers' theory proved correct. They started with a modified version of TAK-779, which didn't include the harmful ammonium salt. After testing, they found that attaching 12 molecules of the modified drug (SDC-1721) to one nanoparticle of gold restored the drug's ability to prevent HIV infection in primary cultured patient cells. When only one molecule of the drug was attached to the gold nanoparticle, the compound was unable to prevent HIV infection, indicating that the multivalency of the drug was important for its activity.
"We've discovered a non-harmful way to improve the strength and efficacy of an important drug," Melander says. "There's no reason to think that this same process can't be used with similar effect on other existing drugs."
North Carolina State University
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For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options.
New Synthetic Molecules Trigger Immune Response to HIV and Prostate Cancer
Researchers at Yale University have developed synthetic molecules capable of enhancing the body's immune response to HIV and HIV-infected cells, as well as to prostate cancer cells. Their findings, published online in the Journal of the American Chemical Society, could lead to novel therapeutic approaches for these diseases.
Common Pain Relievers May Dilute Power of Flu Shots
With flu vaccination season in full swing, research from the University of Rochester Medical Center cautions that use of many common pain killers - Advil, Tylenol, aspirin - at the time of injection may blunt the effect of the shot and have a negative effect on the immune system.
American Dietetic Association Releases Updated Position Paper Promoting and Supporting Breastfeeding
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Daily dose of color may boost immunity this flu season
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Immune therapy can protect against or treat later lymphoma
Specially developed immune system cells that target the common Epstein-Barr virus can protect immune-suppressed bone marrow transplant recipients against lymph system disease and cancers that arise from the viral infection.
PATH Malaria Vaccine Initiative shares strategy for developing 'next-generation' malaria vaccines
Marking its tenth anniversary year, the PATH Malaria Vaccine Initiative (MVI) today unveiled a new strategy that sets the stage for an aggressive push targeting the long-term goal of eliminating and eradicating malaria. Malaria is one of the world's deadliest infectious diseases, killing nearly 900,000 people a year, most of them children in sub-Saharan Africa.
Study reveals a 'missing link' in immune response to disease
The immune system's T cells have the unique responsibilities of being both jury and executioner. They examine other cells for signs of disease, including cancers or infections, and, if such evidence is found, rid them from the body. Precisely how T cells shift so swiftly from one role to another, however, has been a mystery.
Smokers with common autoimmune disorder at higher risk for skin damage
As if there weren't enough reasons to stop smoking, a team of researchers at the Research Institute of the McGill University Health Centre (RI-MUHC) have just found another.
Breakthrough in fight against Hendra virus
There has been a breakthrough in the fight against the deadly Hendra virus following the development of a treatment which shows great potential to save the lives of people who become infected with the virus.
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