The synthesis and testing of inhibitors for the enzyme GTP-cyclohydrolase (I)

Abstract

This thesis investigates the design and synthesis of compounds to be tested as inhibitors of the enzyme guanosine triphosphate cyclohydrolase (I), an enzyme which plays an important role in the biosynthesis of almost all pteridines found in nature, including the folates. It catalyses the conversion o f GT P to dihydroneopterin triphosphate through a number of intermediates. In chapter one a brief account of the importance o f GTP-cyclohydrolase (I) is given in the introduction together with a description of the residues involved at the active site. On the basis of this information we identified several target compounds including 3-deazaguanosine, 8-aza-7-deazaguanosine and 8-azaguanosine.