Fighting Oxidative Damage with Buckyballs

Donald Wolff
Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey
P01ES06897

Background: Nitric oxide (NO), an important regulator of mammalian physiology, serves as a neurotransmitter, regulates blood pressure and flow, and defends against foreign organisms. It is formed by the interaction of the amino acid arginine and the enzyme nitric oxide synthase. Under specific circumstances, NO can be produced in quantities that are harmful. Overproduction of NO has been implicated in septic shock, and in autoimmune diseases such as multiple sclerosis and arthritis. In the neurological system, too much NO has been implicated in tissue damage following stroke and in chronic neurodegenerative disorders. Consequently, many laboratories are directing research to developing inhibitors of various forms of nitric oxide synthase.

Fullerenes, also known as Buckyballs, are a third form of pure carbon after diamonds and graphite. They were discovered in 1985 and are named for Buckminster Fuller, the designer of the geodesic dome because the structure is very similar in that they are hollow geodesic cages or balls. They exist naturally in the environment and can be created in the laboratory under very high pressure conditions. Fullerenes coupled to a variety of compounds in geometrically different positions can be used to deliver substances to targeted areas in biological systems.

Advance: These investigators describe the use of a Fullerene-monomalonate complex for the selective inactivation of the neuronal form of nitric acid synthase. The inactivation does not occur for other forms of the enzyme. The inhibition occurs as a result of the interaction of the Fullerene complex with neuronal nitric acid synthase to so distort the structure of the enzyme as to prevent the formation of intermediate compounds that lead to NO production.

Implication: This finding describes a unique method for inhibiting NO production by neuronal nitric oxide synthase. Although the studies are a still at a very basic level of research, they demonstrate the potential for Fullerene-based adducts to be used as targeted agents to prevent NO formation and thus its harmful effects under certain circumstances.

Citation: Wolff DJ, Mialkowski K, Richardson CF, Wilson SR. C60-Fullerene monomalonate adducts selectively inactivate neuronal nitric oxide synthase by uncoupling the formation of reactive oxygen intermediates from nitric oxide production. Biochemistry. 2001 Jan 9;40(1):37-45.