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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
Immune System Current Events and Immune System News RSSSurface bacteria maintain skin's healthy balance
On the skin's surface, bacteria are abundant, diverse and constant, but inflammation is undesirable. Research at the University of California, San Diego School of Medicine now shows that the normal bacteria living on the skin surface trigger a pathway that prevents excessive inflammation after injury.
Gene mismatch influences success of bone marrow transplants
A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics.
Measuring and modeling blood flow in malaria
When people have malaria, they are infected with Plasmodium parasites, which enter the body from the saliva of a mosquito, infect cells in the liver, and then spread to red blood cells.
New cancer target for non-Hodgkin's lymphoma
Physician-scientists from Weill Cornell Medical College have discovered a molecular mechanism that may prove to be a powerful target for the treatment of non-Hodgkin's lymphoma, a type of cancer that affects lymphocytes, or white blood cells.
First reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
New findings suggest strategy to help generate HIV-neutralizing antibodies
New discoveries about anti-HIV antibodies may bring researchers a step closer to creating an effective HIV vaccine, according to a new paper co-authored by scientists at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
UAB Researchers Discover Antibody Receptor Identity, Propose Renaming Immune-System Gene
Researchers at the University of Alabama at Birmingham (UAB) have uncovered the genetic identity of a cellular receptor for the immune system's first-response antibody, a discovery that sheds new light on infection control and immune disorders.
New culprit for viral infections among elderly -- an overactive immune response
Researchers at Yale School of Medicine have found that exaggerated responses of the immune system explain why the elderly succumb to viral infections more readily than younger people.
Women at risk from vitamin A deficiency
Almost half of UK women could be suffering from a lack of vitamin A due to a previously undiscovered genetic variation, scientists at Newcastle University have found.
Immune system activated in schizophrenia
Researchers at the Swedish medical university Karolinska Institutet have discovered that patients with recent-onset schizophrenia have higher levels of inflammatory substances in their brains. Their findings offer hope of being able to treat schizophrenia with drugs that affect the immune system.
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