l-Nucleosides as chemotherapeutic agents

Gumina, Giuseppe; Song, Gyu-Yong; Chu, Chung K.

doi:10.1111/j.1574-6968.2001.tb10773.x

Cited by 56 publications

(52 citation statements)

References 29 publications

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“…Related ribonucleosides were reported by Shimizu in 1967 [154] and by Hol and orm in 1969 [155]. The discovery of the antiviral activity of 3TC, which is more active and less toxic than its D-counterpart, attracted considerable interest in the synthesis and the pharmacological activity of L-nucleosides [156][157][158][159][160][161][162]. Their antiviral activity is comparable and even greater than that of their D-counterparts.…”

Section: Synthesis Of 7-deazapurine -L-2'-deoxy-ribonucleosidesmentioning

confidence: 97%

Advances in the Synthesis of 7-Deazapurine - Pyrrolo[2,3-d]pyrimidine 2-Deoxyribonucleosides Including D- and L-Enantiomers, Fluoro Derivatives and 2,3-Dideoxyribonucleosides

Seela¹,

Peng²,

Budow

2007

COC

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Section: Synthesis Of 7-deazapurine -L-2'-deoxy-ribonucleosidesmentioning

confidence: 97%

Advances in the Synthesis of 7-Deazapurine - Pyrrolo[2,3-d]pyrimidine 2-Deoxyribonucleosides Including D- and L-Enantiomers, Fluoro Derivatives and 2,3-Dideoxyribonucleosides

Seela¹,

Peng²,

Budow

2007

COC

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“…Ltd., Hyogo, Japan) (Hayashi et al 2014). L-Ribose has attracted attention as a precursor for the synthesis of L-nucleoside analogs, which have been used as antiviral drugs in the treatment of several viral diseases, such HIV and hepatitis (Gumina et al 2001;Cheng 2001).…”

Section: Introductionmentioning

confidence: 99%

Essentiality of tetramer formation of Cellulomonas parahominis L-ribose isomerase involved in novel L-ribose metabolic pathway

Terami

Yoshida

Uechi

et al. 2015

Appl Microbiol Biotechnol

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L-Ribose isomerase from Cellulomonas parahominis MB426 (CpL-RI) can catalyze the isomerization between L-ribose and L-ribulose, which are non-abundant in nature and called rare sugars. CpL-RI has a broad substrate specificity and can catalyze the isomerization between D-lyxose and D-xylulose, D-talose and D-tagatose, L-allose and L-psicose, L-gulose and L-sorbose, and D-mannose and D-fructose. To elucidate the molecular basis underlying the substrate recognition mechanism of CpL-RI, the crystal structures of CpL-RI alone and in complexes with L-ribose, L-allose, and L-psicose were determined. The structure of CpL-RI was very similar to that of L-ribose isomerase from Acinetobacter sp. strain DL-28, previously determined by us. CpL-RI had a cupin-type β-barrel structure, and the catalytic site was detected between two large β-sheets with a bound metal ion. The bound substrates coordinated to the metal ion, and Glu113 and Glu204 were shown to act as acid/base catalysts in the catalytic reaction via a cis-enediol intermediate. Glu211 and Arg243 were found to be responsible for the recognition of substrates with various configurations at 4- and 5-positions of sugar. CpL-RI formed a homo-tetramer in crystals, and the catalytic site independently consisted of residues within a subunit, suggesting that the catalytic site acted independently. Crystal structure and site-direct mutagenesis analyses showed that the tetramer structure is essential for the enzyme activity and that each subunit of CpL-RI could be structurally stabilized by intermolecular contacts with other subunits. The results of growth complementation assays suggest that CpL-RI is involved in a novel metabolic pathway using L-ribose as a carbon source.

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“…For example, several L-sugars can be used to produce L-nucleoside analogues, which showed increased antiviral activity, better metabolic stability, and more favorable toxicological profiles (12,13). L-Sorbose has been applied to produce the potent glycosidase inhibitor 1-deoxygalactonojirimycin and L-ascorbic acid, known as vitamin C (11,14).…”

Section: Dhap-dependent Aldolases Create Two New Stereogenic Centers mentioning

confidence: 99%

Biosynthesis of l -Sorbose and l -Psicose Based on C—C Bond Formation Catalyzed by Aldolases in an Engineered Corynebacterium glutamicum Strain

Yang

Men

et al. 2015

Appl Environ Microbiol

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The property of loose stereochemical control at aldol products from aldolases helped to synthesize multiple polyhydroxylated compounds with nonnatural stereoconfiguration. In this study, we discovered for the first time that some fructose 1,6-diphosphate aldolases (FruA) and tagatose 1,6-diphosphate (TagA) aldolases lost their strict stereoselectivity when using L-glyceraldehyde and synthesized not only L-sorbose but also a high proportion of L-psicose. Among the aldolases tested, TagA A ldolases are remarkably useful and have been widely investigated for catalyzed COC bond formation (1). The ability to catalyze aldol addition reactions from small chiral polyfunctional molecules and generate up to two new stereogenic centers allows aldolases to synthesize a broad range of both natural and novel polyhydroxylated compounds. Among the aldolase families, dihydroxyacetone-phosphate (DHAP)-dependent aldolases, which utilize DHAP as the donor substrate and accept a broad range of acceptor aldehydes, are widely investigated. Well-known members of this class include fuculose 1-phosphate aldolase (FucA), rhamnulose 1-phosphate aldolase (RhaD), fructose 1,6-diphosphate aldolase (FruA), and tagatose 1,6-diphosphate aldolase (TagA) (2). These enzymes have been used to synthesize several new deoxy or phosphorylated sugars and iminocyclitols (3-5). DHAP-dependent aldolases create two new stereogenic centers at C atoms 3 and 4 ([3S,4R], [3S,4S], [3R,4S], [3R,4R]). FucA, FruA, RhaD, and TagA generally form (3R,4R), (3S,4R), (3R,4S), and (3S,4S) stereoconfigurations, respectively (1, 2). However, some aldolases sometimes lost their strict stereoselectivity at the C-4 stereocenter with some aldehydes as substrates. For example, RhaD aldolase from Escherichia coli catalyzed DHAP and L-glyceraldehyde to form L-fructose (3R,4S). However, D-sorbose (3R,4S) and D-psicose (3R,4R) were formed when using D-glyceraldehyde (6-8). Moreover, FucA aldolase from E. coli catalyzed DHAP and L-glyceraldehyde to form the single product L-tagatose (3R,4R). However, FucA from Thermus thermophilus HB8 generated L-tagatose (3R,4R) and L-fructose (3R,4S) simultaneously from the same substrates. This finding indicated that aldolases had a high level of stereocontrol at C-3; however, the configuration of the stereocenter at C-4 in some cases depended on the particular enzyme and acceptor structure. This aldolase property can be well utilized to synthesize various types of rare sugars. Thus far, no reports have shown this property for FruA aldolase. In addition, TagA aldolases form diastereomer mixtures of product, in which instead of the natural configuration (3S,4S), those of the configuration (3S,4R) predominated (Ͼ90%) (4).L-Sugars, which are one large group of rare sugars, often hold enormous potential for applications in the pharmaceutical industry (9-11). For example, several L-sugars can be used to produce L-nucleoside analogues, which showed increased antiviral activity, better metabolic stability, and more favorable toxicological profiles (12, 1...

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l-Nucleosides as chemotherapeutic agents

Cited by 56 publications

References 29 publications

Advances in the Synthesis of 7-Deazapurine - Pyrrolo[2,3-d]pyrimidine 2-Deoxyribonucleosides Including D- and L-Enantiomers, Fluoro Derivatives and 2,3-Dideoxyribonucleosides

Advances in the Synthesis of 7-Deazapurine - Pyrrolo[2,3-d]pyrimidine 2-Deoxyribonucleosides Including D- and L-Enantiomers, Fluoro Derivatives and 2,3-Dideoxyribonucleosides

Essentiality of tetramer formation of Cellulomonas parahominis L-ribose isomerase involved in novel L-ribose metabolic pathway

Biosynthesis of l -Sorbose and l -Psicose Based on C—C Bond Formation Catalyzed by Aldolases in an Engineered Corynebacterium glutamicum Strain

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