It has been shown that 6-acetyl-7,7-dimethyl-5,6,7,8-tetrahydropteridin-4(3H)-one can act as a competent cofactor for the production of nitric oxide by neuronal nitric oxide synthase (nNOS). More information was sought on the structural features that could contribute to strong binding within the enzyme whilst maintaining a fast electron transfer rate. This study was concerned with expansion at the C2-position of the pteridine scaffold. The evidence suggests that expansion at the C2-position had a deleterious effect with respect to K-m and as a consequence electron transfer rate. Unexpectedly, several lines of evidence suggested that a methyl substituent on nitrogen at C2 reduced the electron density in the pyrimidine and dihydropterin rings.
|Number of pages||9|
|Publication status||Published - Dec 2009|