Flavines, 5-deaza

Oxidative substitutions at ring junction positions in various tetrahydro-5-deaza-pterins (79JA6068) and -flavins (77JA6721) have been studied, e.g. to give (13), and the oxidation-reduction reactions of 5-deazaflavins (e.g. 78CL1177, 80CPB3514) across the 1,5-positions, e.g. (19) (20), are involved in their co-enzymic role in enzymic oxidations (see Section... 

Kurfuerst, M., Macheroux, P., Ghisla, S., and Hastings, J. W. (1989). Bioluminescence emission of bacterial luciferase with 1 -deaza-FMN. Evidence for the noninvolvement of N(l)-protonated flavin species as emitters. Eur. J. Biochem. 181 453 157. 

Selected entries from Methods in Enzymology [vol, page(s)] Determination of FMN and FAD by fluorescence titration with apoflavodoxin, 66, 217 purification of flavin-adenine dinucleotide and coenzyme A on p-acetoxymercurianiline-agarose, 66, 221 a convenient biosynthetic method for the preparation of radioactive flavin nucleotides using Clostridium kluyveri, 66, 227 isolation, chemical synthesis, and properties of roseoflavin, 66, 235 isolation, synthesis, and properties of 8-hydroxyflavins, 66, 241 structure, properties and determination of covalently bound flavins, 66, 253 a two-step chemical synthesis of lumiflavin, 66, 265 syntheses of 5-deazaflavins, 66, 267 preparation, characterization, and coenzymic properties of 5-carba-5-deaza and 1-... 

Cheeseman et al. reported in 1972 the purification and properties of a fluorescent compound from Methanobacterium. Owing to the first visible absorption at 420 nm the unknown compound was called Factor-420. It was not until 1978 till it became clear that the compound is a flavin-like molecule By different physical techniques it could be shown that the molecule is a 5-deaza-FMN derivative (Scheme 2, (70)) where at position 8 the methyl group is replaced by a hydroxy group. In addition, the side chain phosphate group is esterified by a lactyl group which, in turn, is linked to a diglutamyl moiety via a peptide bond. Factor-420 functions as... 

Hydride transfer towards dFl occurs readily, yielding 1,5-H2dFlred, as shown by Briistlein and Bruice (37). This does not mean, however, that flavin behaves like nicotinamide but rather that deaza-flavin is not a flavin but a nicotinamide model. 

Dealkylation, of azolium quaternary salts and betaines, 60, 244 Deazaflavines, bent, 55, 192 5-Deazalumazines, see Pyrido[2,3-(/]pyrimidine-2,4-diones Deaza-purines, -flavines, etc., see the systematically-named ring systems 4-Deazatoxoflavins, syntheses, 55, 182 Dechlorination, catalytic, of chloro-[ 1,2.4]triazolo[ 1,5-a]pyrimidines, 57, 125... 

Figure 3 Coenzymes biosynthesized from GTP. 8, molybdopterin 22, GTP 23, 5-amino-6-ribitylamino-2,4(1 H,3H)-pyrimidinedione 24, riboflavin 25, FMN 26, 5,6-dimethylbenzimidazole 27, precursor Z 28, metal containing pterin 29, dihydroneopterin triphosphate 30, 6-pyruvoyl-tetrahydropterin 31, 6(R)-5,6,7,8-tetrahydrobiopterin 32, dihydroneopterin 33, 6(S)-5,6,7,8-tetrahydrofolate 34, 5,6,7,8-tetrahydromethanopterin 35, 5-deaza-7,8-didemethyl-8-hydroxyribo-flavin 36, coenzyme F42q-...

A mechamsm that involves protonation of the a-carbanion/enamine of HEThDP and subsequent hydride transfer, which has been proposed for several flavine-dependent enzymes (Pollegioni et al., 1997), is unlikely since no kinetic solvent isotope effect is evident for this catalytic step (Pig. 16.7). In accordance, after replacement of PAD by 5-carba-5-deaza-FAD, a PAD analog not catalyzing a transfer of single electrons but functioning as hydride acceptor, no reduction is observed by the HEThDP intermediate in pyruvate oxidase from Lactobacillus plantarum (Tittmann et al., 1998). 

GOX. " Accordingly, the structure shows very few protein interactions available for substrate binding. By replacing the flavin with 8-hydroxy-5-carba-5-deaza FAD and determining the stereochemistry of the reaction, it was shown that glucose reacts on the re face of the flavin. " Modeling the substrate in the active site with the... 

Flavin-dependent oxynitrilase has many properties common to flavoprotein oxidases. The enzyme binds sulfite in an N5 adduct, and one-electron reduction produces anionic semiquinone.The sulfite adduct and one- or two-electron reduced enzyme are inactive, as is apoenzyme, suggesting that the flavin is involved in catalysis. When the flavin is replaced by 5-carba-5-deaza FAD, a low level of activity is retained. " " However, when the enzyme containing the artificial flavin is exposed to H2O2, the isoalloxazine ring system is partially degraded to a redox-inactive heterocyclic system. " After the formation of this redox-inactive flavin derivative, enzyme activity actually increases dramatically, suggesting that the flavin plays a structural role. It is possible that the redox state of the flavin serves a regulatory role, since enzyme activity decreases when the natural flavin is reduced however, this has yet to be proven. 

It is interesting to remember that ethyl i -mandelate was produced in 20 I e.e. in the reduction of ethyl benzoylformate with i -PNPH, whereas / -37 afforded ethyl -mandelate predominantly. The structures of the two reductants are similar but the stereochemical properties are quite different from each other, which indicates that the situation at the transition state of the 1,5-dihydro-5-deaza-flavin system is different from that of PNPH. This is perhaps because of the cyclic structure of 51 and of the presence of several heteroatoms in the molecule. A magnesium ion may be able to interact with these heteroatoms. 

Yoneda F, Kuroda K, Kamishimoto M (1981b) Autorecycling system for reduction of carbonyl compounds to alcohols by 1,5-dihydro-5-deaza-flavins. J Chem Soc Chem Commun 1160-1162... 

Figure 11 HPLC separation of flavin analogs (1) ATP (2) 8-hydroxy-FAD (3) FAD (4) 1-deaza-FAD (5) 5-deaza-FAD (6) FMN (7) 1-deaza-FMN (8) riboflavin (9) 5-deaza-FMN (10) 1 -deaza-riboflavin (11) methyl-riboflavin (12) 5-deaza-riboflavin. Column, Lichrosorb RP18, 25 X 1 cm linear gradient between 5 mM ammonium acetate buffer pH 6.0, and methanol. (From Ref. 85.)...

A high-spin Fe + signal, similar to an oxidized form of rubredoxin, was also detected. After reduction with NADPH and NADH, two iron-sulfur clusters, [4Fe-4S] and [2Fe-2S], were observed by EPR. The [4Fe-4S] cluster, but not the [2Fe-2S] cluster, could also be reduced by dithionite or 5-deaza-flavinyoxalate. A third, and as yet unidentified, iron-sulfur cluster with g = 2.057 was also observed. This could be reduced by dithonite but not by NADH or NADPH. The extremely fast spin-relaxation rates of semiquinone and flavin radicals suggested that they are in close proximity to the [4Fe-4S] cluster or the high-spin Fe " " centre. 

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