Synthesis of 6-amino-2,3-dimethylpyrimido[4,5-e][1,2,4]triazine-8-one as an inhibitor of dihydropteridine reductase (DHPR)

BIOL 253

Jeonghee Kang, jkang@york.cuny.edu and Ruel Z. B. Desamero, desamero@york.cuny.edu. Department of Natural Sciences-Chemistry, York College, the Graduate Center and the Institute of Macromolecular Assembly of CUNY, 94-20 Guy R. Brewer Blvd., Jamaica, NY 11451
Dihydropteridine reductase is an enzyme that catalyses the reduction of quinonoid 7,8-dihydropterin (qBH2) to the corresponding 5,6,7,8-tetrahydropterin (BH4) while utilizing NADH as the hydride source. The reduced BH4 is a cofactor in the conversion of phenylalanine to tyrosine by phenylalanine-4-hydroxylase; the conversion of tyrosine to L-dopa by tyrosine hydroxylase; and conversion of tryptophan to 5-hydroxytryptophan via tryptophan hydroxylase. Understanding how DHPR could be regulated is important since its deficiency cause genetic disorder, phenylketonuria as well as dopa-responsive dystonias. Herein we present the synthesis of the inhibitor for mechanism study in the metabolism associated with NADH and DHPR. Enzymatic mechanism study using IR and Raman spectroscopy is being investigated.
 

Frontiers in Chemical Biology
5:00 PM-7:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biological Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007