The inhibition of purine biosynthesis has been observed with the use of various types of compounds. The antibiotics O-diazoacetyl-n-serine (azaserine) and 6-diazo-5-oxo-n-norleucine suppress purine formation by virtue of their antagonistic action toward glutamine in amination reactions (l-3). Several structural analogues of purine and of pteroylglutamic acid are also known to block the biosynth...

Natural and synthetic purine derivatives such as caffeine, theophylline, 6-mercaptopurine and 8-chlorotheophylline are important drugs. Due to the structural similarity of these compounds, it is intrinsically difficult to prepare chemosensors for their selective optical detection. Here, we describe a sensor array which can be used to differentiate pharmacologically important purine derivatives ...

Base analogs are powerful antimetabolites and dangerous mutagens generated endogenously by oxidative stress, inflammation, and aberrant nucleotide biosynthesis. Human inosine triphosphate pyrophosphatase (ITPA) hydrolyzes triphosphates of noncanonical purine bases (i.e., ITP, dITP, XTP, dXTP, or their mimic: 6-hydroxyaminopurine (HAP) deoxynucleoside triphosphate) and thus regulates nucleotide ...

Gout is classed among the inborn errors of metabolism,1 but unlike the majority of such disorders no single specific metabolic defect has yet been found to account for the hyperuricemia characteristic of this disease.2 Although impaired renal excretion of uric acid is responsible for the hyperuricemia of some patients, an increased rate of purine biosynthesis de novo contributes to the hyperuri...

Plasmodium falciparum causes most of the one million annual deaths from malaria. Drug resistance is widespread and novel agents against new targets are needed to support combination-therapy approaches promoted by the World Health Organization. Plasmodium species are purine auxotrophs. Blocking purine nucleoside phosphorylase (PNP) kills cultured parasites by purine starvation. DADMe-Immucillin-...

A unified synthetic strategy accessing novel 3'-fluorinated purine nucleoside derivatives and their biological evaluation were achieved. Novel 3'-fluorinated analogues were constructed from a common 3'-deoxy-3'-fluororibofuranose intermediate. Employing Suzuki and Stille cross-coupling reactions, fifteen 3'-fluororibose purine nucleosides 1-15 and eight 3'-fluororibose 2-chloro/2-aminopurine nu...

On-line sample preconcentration by a dynamic pH junction in conjunction with multiplexed capillary electrophoresis (CE) and UV detection represents a sensitive and high-throughput format for future metabolomic research, such as purine analysis. The optimization of purine focusing can be rapidly assessed by systematically altering the sample matrix properties, such as the buffer co-ion, pH and i...

To evaluate cellular uptake and purine transport, we developed a high-performance liquid chromatography method for intra- and extracellular purine quantification. Our aim was to develop an effective method for simultaneously quantifying the substrate and metabolites with high sensitivity. C18 columns from different manufacturers were tested for simultaneous quantification of 22 different purine...

Purine biosynthesis by the 'de novo' pathway was demonstrated in isolated rat extensor digitorum longus muscle with [1-14C]glycine, [3-14C]serine and sodium [14C]formate as nucleotide precursors. Evidence is presented which suggests that the source of glycine and serine for purine biosynthesis is extracellular rather than intracellular. The relative incorporation rates of the three precursors w...