Chiral lumazines: Preparation, properties, enantiomeric separation

Abstract

Optically active lumazines (biolumazine, dictyolumazine, monalumazine, and neolumazine) are prepared from the corresponding pterins by enzymatic reaction, using pterin deaminase excreted by Dictyostelium discoideum. The fluorescence properties, circular dichroism spectra, and chromatographic behavior of these lumazines are studied. D- and L-enantiomers of biolumazine, dictyolumazine, and monalumazine are separated using a chiral flavoprotein column. This column also separates the enantiomeric pterins of the threo form: monapterin and dictyopterin. However, the column does not separate the enantiomeric pterins of the erythro form: neopterin and biopterin. By coupling a reverse-phase column to the flavoprotein column, the separation of pterins and lumazines in function of their hydrophobicity, as well as the separation of the diastereomers, is achieved. This coupled achiral/chiral high-performance liquid chromatography method enables determination of the stereoconfiguration of natural lumazines by comparison with optically pure compounds. A lumazine derivative, present in the extracellular medium of Dictyostelium discoideum, is identified as D-dictyolumazine, i.e., 6-(D-threo-1,2-dihydroxypropyl)-lumazine.

Molecular cloning of a cDNA coding for GTP cyclohydrolase I from Dictyostelium discoideum

“…This process is controlled by cAMP, whose signal transduction is linked to heterotrimeric G-proteins [10,11]. Recently, we have shown that tetrahydrodictyopterin [12,13], the threo-isomer of BH % , originates from GTP by de no o biosynthesis requiring the action of GTP-CH [14]. During the developmental process the activity of GTP-CH is regulated independently in the cytosolic and membrane fractions.…”

Naturally Occurring Lumazines

“…30 Dictyolumazine (38) was observed in the media of starved Dictyostelium discoideum and identified by comparison to a semisynthetic chiral standard using chiral HPLC. 64,65 Dictyolumazine (38) was demonstrated to be responsible for the extracellular fluorescence linked with the aggregation ability of D. discoideum cells. 64 No other biological properties were reported for chiral lumazines 34−38.…”

“…The 1′ S ,2′ R -configuration of dihydroxylumazine 37 was determined by diacetylation of the compound and comparison of its spectroscopic data with those of a semisynthetic sample . Dictyolumazine ( 38 ) was observed in the media of starved Dictyostelium discoideum and identified by comparison to a semisynthetic chiral standard using chiral HPLC. , Dictyolumazine ( 38 ) was demonstrated to be responsible for the extracellular fluorescence linked with the aggregation ability of D. discoideum cells . No other biological properties were reported for chiral lumazines 34 – 38 .…”

Control of 6-(d-threo-1′,2′-dihydroxypropyl) pterin (dictyopterin) synthesis during aggregation of Dictyostelium discoideum. Involvement of the G-protein-linked signalling pathway in the regulation of GTP cyclohydrolase I activity

“…It was named dictyopterin and represents a new naturally occurring isomer of -biopterin [28]. It was also shown that dictyopterin is deaminated by an extracellular pterin deaminase to -threo-1,2-dihydroxypropyl lumazine (-dictyolumazine) [29].…”