1,721,999 research outputs found
The crystal structure of the Y140F mutant of ADP-L-glycero-D-manno-heptose 6-epimerase bound to ADP-beta-D-mannose suggests a one base mechanism
No full textSupported by Wellcome Trust grant 081862/Z/06/ZBacteria synthesize a wide array of unusual carbohydrate molecules, which they use in a variety of ways. The carbohydrate L-glycero-D-manno-heptose is an important component of lipopolysaccharide and is synthesized in a complex series of enzymatic steps. One step involves the epimerization at the C6 '' position converting ADP-D-glycero-D-manno-heptose into ADP-L-glycero-D-manno-heptose. The enzyme responsible is a member of the short chain dehydrogenase superfamily, known as ADP-L-glycero-D-manno-heptose 6-epimerase (AGME). The structure of the enzyme was known but the arrangement of the catalytic site with respect to the substrate is unclear. We now report the structure of AGME bound to a substrate mimic, ADP-beta-D-mannose, which has the same stereochemical configuration as the substrate. The complex identifies the key residues and allows mechanistic insight into this novel enzyme.Peer reviewe
High-throughput virtual screening and molecular dynamics simulation reveals NPC170742 a novel chalconoid compound as a potential inhibitor of D-glycero-D-manno-heptose-1,7-bisphosphate 7-phosphatase in <i>Helicobacter pylori</i>
No full textHelicobacter pylori is a gram negative spiral shaped bacteria that causes peptic ulcer and gastric cancer. It Is the sixth most prevalent cancer in the world and the third leading cause of cancer death. The increase in reported cases of H. pylori resistance to the drugs and antibiotics shows the need for the development of new and efficient drugs against the pathogen. In the present study, D-glycero-D-manno-heptose-1,7-bisphosphate 7-phosphatase (GmhB), an enzyme involved in the biosynthesis of lipopolysaccharides that encourages bacterial adherence, self-aggregation and identifying the host cells was modelled and the active sites were predicted through POCASA which is an automated ligand binding site prediction server. Natural product activity and species source (NPASS) is a database of 96,481 natural compounds that were subjected to virtual screening workflow that includes Qikprop, Lipinski rule, filtering out reactive functional groups followed by high throughput virtual screening and the top 10 compounds were selected for further induced fit docking along with the substrate D-glycero-β-D-manno-heptose 1,7-bisphosphate. The compound NPC170742 (Alpha, Beta, 3,4,5,2′,4′,6′-Octahydroxy dihydrochalcone) showed higher affinity than the substrate, and both the substrate D-glycero-β-D-manno-heptose 1,7-bisphosphate and the compound NPC170742 were subjected to molecular dynamics simulation. The results exposed the compound NPC170742 could be a potential lead compound against the enzyme D-glycero-D-manno-heptose-1,7-bisphosphate 7-phosphatase of H. pylori. Communicated by Ramaswamy H. Sarma</p
Highly Diastereoselective 1,4-Addition of an Organocuprate to Methyl α-d-Gluco-, α-d-Manno-, or α-d-Galactopyranosides Tethering an α,β-Unsaturated Ester. Novel Asymmetric Access to β-C-Substituted Butanoic Acids
No full textThe 1,4-addition of magnesium divinylcuprate prepared from vinylmagnesium bromide and cuprous
bromide to some 4-O-crotonyl derivatives of methyl α-d-glucopyranoside proceeds with a high level
of diastereochemical induction, providing the adduct in good-to-excellent yields. Other organocuprates also serve as effective carbon nucleophiles for the 1,4-addition. Removal of the carbohydrate
moiety from each adduct afforded a variety of β-C-substituted butanoic esters in remarkable
enantiomeric excess. The 1,4-addition of the same cuprate to some methyl α-d-manno- or α-d-galactopyranosidic substrates in which a crotonyl group was incorporated, each at 3-OH, was also
investigated. The reverse π-facial attack of the cuprate was observed when some d-manno-type
substrates were subjected to 1,4-addition conditions similar to those used for the d-gluco-type
substrates. Furthermore, some d-galacto-type substrates provided 1,4-adducts with higher diastereoselectivities
Highly Diastereoselective 1,4-Addition of an Organocuprate to Methyl α-d-Gluco-, α-d-Manno-, or α-d-Galactopyranosides Tethering an α,β-Unsaturated Ester. Novel Asymmetric Access to β-C-Substituted Butanoic Acids
No full textThe 1,4-addition of magnesium divinylcuprate prepared from vinylmagnesium bromide and cuprous
bromide to some 4-O-crotonyl derivatives of methyl α-d-glucopyranoside proceeds with a high level
of diastereochemical induction, providing the adduct in good-to-excellent yields. Other organocuprates also serve as effective carbon nucleophiles for the 1,4-addition. Removal of the carbohydrate
moiety from each adduct afforded a variety of β-C-substituted butanoic esters in remarkable
enantiomeric excess. The 1,4-addition of the same cuprate to some methyl α-d-manno- or α-d-galactopyranosidic substrates in which a crotonyl group was incorporated, each at 3-OH, was also
investigated. The reverse π-facial attack of the cuprate was observed when some d-manno-type
substrates were subjected to 1,4-addition conditions similar to those used for the d-gluco-type
substrates. Furthermore, some d-galacto-type substrates provided 1,4-adducts with higher diastereoselectivities
Highly Diastereoselective 1,4-Addition of an Organocuprate to Methyl α-d-Gluco-, α-d-Manno-, or α-d-Galactopyranosides Tethering an α,β-Unsaturated Ester. Novel Asymmetric Access to β-C-Substituted Butanoic Acids
No full textThe 1,4-addition of magnesium divinylcuprate prepared from vinylmagnesium bromide and cuprous
bromide to some 4-O-crotonyl derivatives of methyl α-d-glucopyranoside proceeds with a high level
of diastereochemical induction, providing the adduct in good-to-excellent yields. Other organocuprates also serve as effective carbon nucleophiles for the 1,4-addition. Removal of the carbohydrate
moiety from each adduct afforded a variety of β-C-substituted butanoic esters in remarkable
enantiomeric excess. The 1,4-addition of the same cuprate to some methyl α-d-manno- or α-d-galactopyranosidic substrates in which a crotonyl group was incorporated, each at 3-OH, was also
investigated. The reverse π-facial attack of the cuprate was observed when some d-manno-type
substrates were subjected to 1,4-addition conditions similar to those used for the d-gluco-type
substrates. Furthermore, some d-galacto-type substrates provided 1,4-adducts with higher diastereoselectivities
Highly Diastereoselective 1,4-Addition of an Organocuprate to Methyl α-d-Gluco-, α-d-Manno-, or α-d-Galactopyranosides Tethering an α,β-Unsaturated Ester. Novel Asymmetric Access to β-C-Substituted Butanoic Acids
No full textThe 1,4-addition of magnesium divinylcuprate prepared from vinylmagnesium bromide and cuprous
bromide to some 4-O-crotonyl derivatives of methyl α-d-glucopyranoside proceeds with a high level
of diastereochemical induction, providing the adduct in good-to-excellent yields. Other organocuprates also serve as effective carbon nucleophiles for the 1,4-addition. Removal of the carbohydrate
moiety from each adduct afforded a variety of β-C-substituted butanoic esters in remarkable
enantiomeric excess. The 1,4-addition of the same cuprate to some methyl α-d-manno- or α-d-galactopyranosidic substrates in which a crotonyl group was incorporated, each at 3-OH, was also
investigated. The reverse π-facial attack of the cuprate was observed when some d-manno-type
substrates were subjected to 1,4-addition conditions similar to those used for the d-gluco-type
substrates. Furthermore, some d-galacto-type substrates provided 1,4-adducts with higher diastereoselectivities
Biosynthesis of Nucleotide-activatedd-glycero-d-manno-Heptose
No full textThe glycan chain repeats of the S-layer glycoprotein of Aneurinibacillus thermoaerophilus DSM 10155 contain D-glycero-D-manno-heptose, which has also been described as constituent of lipopolysaccharide cores of Gram-negative bacteria. The four genes required for biosynthesis of the nucleotide-activated form GDP-D-glycero-D-manno-heptose were cloned, sequenced, and overexpressed in Escherichia coli, and the corresponding enzymes GmhA, GmhB, GmhC, and GmhD were purified to homogeneity. The isomerase GmhA catalyzed the conversion of D-sedoheptulose 7-phosphate to D-glycero-D-manno-heptose 7-phosphate, and the phosphokinase GmhB added a phosphate group to form D-glycero-D-manno-heptose 1,7-bisphosphate. The phosphatase GmhC removed the phosphate in the C-7 position, and the intermediate D-glycero-α-D-manno-heptose 1-phosphate was eventually activated with GTP by the pyrophosphorylase GmhD to yield the final product GDP-D-glycero-α-D-manno-heptose. The intermediate and end products were analyzed by high performance liquid chromatography. Nuclear magnetic resonance spectroscopy was used to confirm the structure of these substances. This is the first report of the biosynthesis of GDP-D-glycero-α-D-mannoheptose in Gram-positive organisms. In addition, we propose a pathway for biosynthesis of the nucleotide-activated form of L-glycero-D-manno-heptose
Formal Synthesis of 3-Deoxy-d-manno-2-Octulosonic Acid (KDO) via a Highly Double-Stereoselective Hetero Diels−Alder Reaction Directed by a (Salen)Co<sup>II</sup> Catalyst and Chiral Diene
No full textThis paper presents a formal total synthesis of
3-deoxy-d-manno-2-octulosonic acid (KDO) based
on a highly double-stereoselective hetero Diels−Alder reaction
between an electron-rich diene and
ethyl glyoxylate catalyzed by (Salen)CoII complex, a new
catalyst for Diels−Alder reactions. A
facial specific hydroboration followed by oxidative workup leads to a
diol system with the trans-diequatorial arrangement of hydroxyl groups at the C-4 and C-5.
Inversion of the configuration of
the C-5 hydroxyl group in 12 and then ketal formation afford
the desired target diisopropylidene-2-deoxy-KDO methyl ester (18), which can be converted to KDO
according to the literature
procedure
Crystal and molecular structure of methyl l-glycero-α-d-manno-heptopyranoside, and synthesis of 1→7 linked l-glycero-d-manno-heptobiose and its methyl α-glycoside
No full textAbstractMethyl l-glycero-α-d-manno-heptopyranoside was synthesized in good yield by a Fischer-type glycosylation of the heptopyranose with methanol in the presence of cation-exchange resin under reflux and microwave conditions, respectively. The compound crystallized from 2-propanol in an orthorhombic lattice of space group P21212 showing a comparatively porous structure with a 2-dimensional O–H⋯O hydrogen bond network. As model compounds for the side chain domains of the inner core structure of bacterial lipopolysaccharide, l-glycero-α-d-manno-heptopyranosyl-(1→7)-l-glycero-d-manno-heptopyranose and the corresponding disaccharide methyl α-glycoside were prepared. The former compound was generated via glycosylation of a benzyl 5,6-dideoxy-hept-5-enofuranoside intermediate followed by catalytic osmylation and deprotection. The latter disaccharide was efficiently synthesized in good yield by a straightforward coupling of an acetylated N-phenyltrifluoroacetimidate heptopyranosyl donor to a methyl 2,3,4,6-tetra-O-acetyl heptopyranoside acceptor derivative followed by Zemplén deacetylation
Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction
No full textA [4 + 3] synthesis of D-manno-heptulose is described. The cascade aldol/hemiketalization reaction of a C4 aldehyde with a C3 ketone provides the differentially protected ketoheptose building block, which can be further reacted to furnish target D-manno-heptulose
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