- Synthesis and conformational analysis of D-gluco-pyranosyl-(6,6′)-D-gluco-pyranuronate, a model compound for the inter-glycan 6,6′-ester linkage
-
The synthesis of a 6,6′-ester linked disaccharide analog model compound was achieved in five steps from D-glucose and featured a key oxidative esterification transformation. The synthesized D-gluco-pyranosyl-(6,6′)-D-gluco-pyranuronate was characterized in D2O using NMR spectroscopy. Using the experimental data together with molecular dynamics simulations (TIP3P, water), a model of the compound's conformational behavior was established. The effect of the 6,6′-ester linkage on the solution phase structure was compared to that of the previously reported 6,6′-ether linkage in a disaccharide analog. Based on the established models, the ester linkage was found to have a profound effect on the overall shape of the molecule.
- Hackbusch, Sven,Watson, Amelia,Franz, Andreas H.
-
-
Read Online
- INHIBITORS OF MALARIAL AND PLASMODIUM FALCIPARUM HEXOSE TRANSPORTER AND USES THEREOF
-
Provided are molecules capable of binding to binding pockets of Plasmodium falciparum hexose transporter (PfHT) or analogs thereof and complexes comprising the same. Also provided herein are inhibitors of PfHT, pharmaceutical compositions comprising the i
- -
-
Paragraph 00504; 00506
(2021/08/14)
-
- New class of alkynyl glycoside analogues as tyrosinase inhibitors
-
A new series of alkynyl glycoside analogues were designed and synthesized from cheap and a commercially available sugar by introduction of various alkynyl and alkyl groups at C-1 and C-6 positions of the sugar ring. The inhibitory abilities of alkynyl gly
- Saehlim, Natthiya,Athipornchai, Anan,Sirion, Uthaiwan,Saeeng, Rungnapha
-
supporting information
(2020/06/01)
-
- Addressing the biochemical foundations of a glucose-based "trojan horse"-strategy to boron neutron capture therapy: From chemical synthesis to in vitro assessment
-
Boron neutron capture therapy (BNCT) for cancer is on the rise worldwide due to recent developments of in-hospital neutron accelerators which are expected to revolutionize patient treatments. There is an urgent need for improved boron delivery agents, and herein we have focused on studying the biochemical foundations upon which a successful GLUT1-targeting strategy to BNCT could be based. By combining synthesis and molecular modeling with affinity and cytotoxicity studies, we unravel the mechanisms behind the considerable potential of appropriately designed glucoconjugates as boron delivery agents for BNCT. In addition to addressing the biochemical premises of the approach in detail, we report on a hit glucoconjugate which displays good cytocompatibility, aqueous solubility, high transporter affinity, and, crucially, an exceptional boron delivery capacity in the in vitro assessment thereby pointing toward the significant potential embedded in this approach.
- Ekholm, Filip S.,Matovic, Jelena,Jarvinen, Juulia,Bland, Helena C.,Sokka, Iris K.,Imlimthan, Surachet,Huttunen, Kristiina M.,Timonen, Juri,Peraniemi, Sirpa,Aitio, Olli,Airaksinen, Anu J.,Sarparanta, Mirkka,Johansson, Mikael P.,Rautio, Jarkko
-
p. 3885 - 3899
(2020/11/12)
-
- A novel selectfluor-mediated regioselective O-benzyl ether acetolysis of perbenzylated monosaccharides
-
Selectfluor, a source of the super electrophile F+, has replaced conventional reagents that supply F+ for fluorination due to its attractive physical and chemical properties. This study is the first report of using Selectfluor as a d
- Tambie, Marlon S.,Jalsa, Nigel Kevin
-
p. 545 - 559
(2016/04/19)
-
- ELECTROCHEMICAL METHODS AND COMPOUNDS FOR THE DETECTION OF ENZYMES
-
Disclosed are compositions and methods for the electrochemical detection of enzymes, such as enzymes that are indicative of disease, disorders, or pathogens, such as viruses, bacteria, and fungi, or other disorders. These methods can be used in point-of- care diagnostic assays for the detection of disease, disorder, or pathogen (e.g., to identify the strain of pathogen infecting a patient in a healthcare setting). The electrochemical methods described herein can also be used to assess the susceptibility of a pathogen to an antipathogen drug. Also provided are probes suitable for use in conjunction with the methods described herein.
- -
-
-
- Electrochemical assay to detect influenza viruses and measure drug susceptibility
-
An electrochemical assay has been designed to rapidly diagnose influenza viruses. Exposure of a glucose-bearing substrate to influenza viruses or its enzyme, neuraminidase (NA), releases glucose, which was detected amperometrically. Two methods were used
- Zhang, Xiaohu,Dhawane, Abasaheb N.,Sweeney, Joyce,He, Yun,Vasireddi, Mugdha,Iyer, Suri S.
-
p. 5929 - 5932
(2015/05/13)
-
- AMPHETAMINE PRODRUGS
-
The present invention relates to amphetamine prodrugs which provide colonic release of amphetamine.
- -
-
-
- Design, synthesis and biological evaluation of multivalent glucosides with high affinity as ligands for brain targeting liposomes
-
The new bifunctional cluster glucosides were designed and synthesized as liposome ligands for preparing novel liposome to achieve the effective delivery of drug formulations to brain by GLUT1. Docetaxel-loaded five liposomes were prepared successfully and tested in the animals. Results from the in vivo distribution study after i.v. administration of these five liposomes and blank-docetaxel indicated that the coupled liposomes Lip-1, Lip-2, Lip-3, Lip-5 exhibited excellent transport ability across the BBB. In particular, they significantly increased the level of docetaxel in brain compared to blank-docetaxel and Lip. Among them, Lip-5 showed higher brain concentration. Both pharmacokinetics and distribution study in mice confirmed that this novel brain targeting drug delivery system was a promising carrier to enhance brain delivery capacity for CNS drugs.
- Qu, Boyi,Li, Xiaocen,Guan, Mei,Li, Xun,Hai, Li,Wu, Yong
-
p. 110 - 118
(2014/01/06)
-
- COMPOUNDS AND COMPOSITIONS FOR THE DETECTION AND TREATMENT OF ALZHEIMER'S DISEASE AND RELATED DISORDERS
-
One aspect of the present invention relates to compounds, compositions and methods for diagnosis and/or treatment of a subject suffering from an amyloidosis-associated pathological condition. In certain embodiments, the imaging and/or therapeutic agents of the instant invention may be administered to a subject for identification and/or treatment of amyloid deposits. A specific imaging method detects amyloid deposits by administering the imaging agent to the subject and detecting the spatial distribution of the agent. Differential accumulation of the agent is indicative of AD or an amyIoidosis-associated pathological condition and can be monitored by using a PET or SPECT camera.
- -
-
-
- Synthesis of cyclophospho-glucoses and glucitols
-
The syntheses of cyclophosphodiesters of 5-C-(hydroxymethyl)-hexoses and hexitols and of 6-C-(hydroxymethyl)-hexoses are reported, along with that of 6-deoxy-gluco-heptose 7-phosphate. These compounds proved to be reasonable substrate mimics and show inhibitory activity against human d-myo-inositol 3-phosphate synthase.
- Amigues,Greenberg,Ju,Chen,Migaud
-
p. 10042 - 10053
(2008/02/13)
-
- An expedient synthesis of benzyl 2,3,4-tri-O-benzyl-β-D- glucopyranoside and benzyl 2,3,4-tri-O-benzyl-β-D-mannopyranoside
-
An efficient three-step synthesis of benzyl 2,3,4-tri-O-benzyl-β-d- glucopyranoside, a widely used building block in carbohydrate chemistry, is described. The key step is the selective debenzylation-acetylation of perbenzylated β-glucose using ZnCl2
- Lu, Wallach,Navidpour, Latifeh,Taylor, Scott D.
-
p. 1213 - 1217
(2007/10/03)
-
- Synthesis of glycosyl derivatives as dopamine prodrugs: Interaction with glucose carrier GLUT-1
-
Glucosyl dopamine (DA) derivatives may represent a new class of DA prodrugs that would interact with glucose transporter GLUT-1, present in the blood-brain barrier, and generate DA in the brain. Therefore, compounds bearing the sugar moiety linked to eith
- Fernandez, Caridad,Nieto, Ofelia,Fontenla, Jose Angel,Rivas, Emilia,De Ceballos, Maria L.,Fernandez-Mayoralas, Alfonso
-
p. 767 - 771
(2007/10/03)
-
- Synthesis of oligomeric assemblies of a platelet-binding key disaccharide in heparin and their biological activities
-
Heparin, highly sulfated glycosaminoglycan, binds to platelets. A key disaccharide unit in heparin was previously found to be responsible for the binding, and the frequency of the disaccharide unit was important for the binding potency. A newly developed method based on the reductive amination was effectively applied to prepare structurally defined oligomeric assemblies possessing multiple units of the key disaccharide. From their platelet-binding activities measured by the competitive binding assay, the enhancement of the activity was clearly observed with increasing number of the key disaccharide.
- Koshida, Shuhei,Suda, Yasuo,Sobel, Michael,Kusumoto, Shoichi
-
p. 1289 - 1292
(2007/10/03)
-
- α-Fluorinated phosphonates as substrate mimics for glucose 6-phosphate dehydrogenase: The CHF stereochemistry matters
-
Reported is a systematic study of the 'fitness' (in terms of k(cat)/K(m)) of a series of phosphonate mimics of glucose 6-phosphate (G6P) as unnatural substrates for G6P dehydrogenase from Leuconostoc mesenteroides. The four G6P analogues (9, 10, 15a, and 15b) differ only in the degree of fluorination at the 'bridging' phosphonate carbon. All have been synthesized from benzyl 6-O-trifluoromethane-sulfonyl-2,3,4-tri-O-benzyl β-D-glucopyranoside (6). The phosphonates with bridging CH2 (9) and CF2 (10) groups are cleanly obtained by direct displacements with the appropriate LiX2CP(O)(OEt)2 reagents (X = H, F) in 15 min at -78 °C. For the (α-monofluoro)alkylphosphonates (15a/b), homologation of 6 is achieved via lithiodithiane-mediated triflate displacement, followed by aldehyde unmasking [CaCO3, Hg(ClO4)2, H2O]. Addition of diethyl phosphite anion produces diastereomeric, (α-hydroxy)phosphonates 13a/b (1.4:1 ratio) which may be readily separated by chromatography. The stereochemistry of the minor diastereomer was established as 7(S) via X-ray crystallographic structure determination of its p-bromobenzoate derivative, 16b. Treatment of the major 7(R) diastereomer with DAST produces α-fluorinated phosphonate 14a, in modest yield, with inversion of configuration, as established, again, by X-ray crystallography. To our knowledge, this is first example of DAST-mediated fluorination of a (nonbenzylic, nonpropargylic) secondary (α-hydroxy)-phosphonate and thus establishes the stereochemical course of this transformation. α-Deprotonation/kinetic quenching of 14a provides access to the 7(R)-epimer (14b). For all four protected phosphonates (7, 8, 14a, and 14b), diethyl phosphonate ester deprotection was carried out with TMSBr, followed by global hydrogenolytic debenzylation to produce the free phosphonates, as α/β anomeric mixtures. Titrations of G6P itself and the free phosphonic acids provides second pK(a) values of 6.5 (1, bridging-O), 5.4 (10, bridging-CF2), 6.2 (14a, bridging-CHF), and 7.6 (9, bridging-CH2). Leuconostoc mesenteroides G6PDH-mediated oxidation and Lineweaver-Burk analysis yields normalized k(cat)/K(m) values of 0.043 (14b, bridging-7(R)-CHF), 0.11 (10, bridging-CF2), 0.23 (14b, bridging-CH2), and 0.46 (14a, bridging-7(S)-CHF) relative to G6P itself, largely reflecting differences in K(m). The fact that k(cat)/K(m) increases by more than an order of magnitude in going from the 7(R)-α-monofluoroalkyl phosphonate (worst substrate) to the 7(S)-diastereomer (best substrate) is especially notable and is discussed in the context of the known phosphate binding pocket of this enzyme as revealed by X-ray crystallography (Adams, M. J. et al. Structure 1994, 2, 1073-1087).
- Berkowitz, David B.,Bose, Mohua,Pfannenstiel, Travis J.,Doukov, Tzanko
-
p. 4498 - 4508
(2007/10/03)
-
- The use of a new magnesium-derived hydride reagent for carbohydrate derivatives
-
The magnesium hydride based reagent in THF solution is an excellent tool for the stereoselective reduction of different uloside derivatives. Sugar azides, sulfonyl esters give aminosugars and methylose derivatives without affecting other functionalities. Halogenated sugars or methylene derivatives are stable under these conditions. The reagent can be applied in the presence of a wide variety of blocking groups (acetals, benzyl and allyl ethers, imides, C=C bonds) generally used in the carbohydrate chemistry.
- Szabovik,Medgyes,Antal,Varga,Knott,Liptak
-
p. 1003 - 1009
(2007/10/03)
-
- Novel carbocyclic ring closure of hex-5-enopyranosides
-
Retention of configuration at the anomeric carbon atom is observed for a novel rearrangement of carbohydrates. The readily accessible vinyl acetal 1 undergoes a triisobutylaluminum-assisted, stereoselective transposition of an oxygen atom on the ring with
- Das,Mallet,Sinay
-
p. 493 - 496
(2007/10/03)
-
- Synthesis of 4-O and 6-O-β-D-xylopyranosyl-D-glucopyranoses and their protein conjugates
-
Benzyl 2,3,6-tri-O-benzyl-β-D-glucopyranoside (7) and benzyl 2,3,4-tri-O-benzyl-β-D-glucopyranoside (8) have been synthesized from D-glucose in seven steps.D-Xylosylation (Koenigs-Knorr) of these compounds gives benzyl 4-O-(2,3,4-tri-O-acetyl-β-D-xylopyranosyl)-2,3,4-tri-O-benzyl-β-D-glucopyranoside (9) and benzyl 6-O-(2,3,4-tri-O-acetyl-β-D-xylopyranosyl)-2,3,4-tri-O-benzyl-β-D-glucopyranoside (10) respectively.Subsequent deacetylation and hydrogenolysis affords 4-O-β-D-xylopyranosyl-D-glucose (13) and 6-O-β-D-xylopyranosyl-D-glucose (14) respectively.Thesedisaccharides have been coupled to human serum albumin by reductive amination procedure.
- Sen, Asish K.,Banerji, Nilima
-
p. 818 - 823
(2007/10/02)
-
- SYNTHESIS OF CELLOBIOSE, CELLOTRIOSE, CELLOTETRAOSE, AND LACTOSE
-
Condensation of 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (1) with benzyl 2,3,6-tri-O-benzyl-β-D-glucopyranoside (6) in 1:1 benzene-nitromethane in the presence of mercuric cyanide gave, in 86percent yield after O-deacetylation followed by column chromatography, benzyl 2,3,6-tri-O-benzyl-β-cellobioside, which was catalytically hydrogenolyzed to afford cellobiose.In a similar way, methyl-α-cellobioside cellotriose, methyl-α- and β-cellotriosides, cellotetraose, lactose, and methyl α-lactoside were synthesized with high stereospecificity and in good yield by the coupling reaction, using methyl 2,3,6-tri-O-benzyl-α- and -β-D-glucopyranosyde, 6, and benzyl 2,3,6,2',3',6'-hexa-O-benzyl-β-cellobioside as the glycosyl acceptors, and 1, 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide, and hepta-O-acetyl-α-cellobiosyl bromide as the glycosyl donors.
- Takeo, Ken'ichi,Okushio, Kazuo,Fukuyama, Katsumi,Kuge, Takashi
-
p. 163 - 174
(2007/10/02)
-
- THE REGIOSELECTIVITY OF THE REDUCTIVE RING-CLEAVAGE OF THE ACETAL RING OF 4,6-O-BENZYLIDENEHEXOPYRANOSIDES
-
The hydrogenolytic ring-cleavage of benzyl 4,6-O-benzylidene-β-D-glucopyranoside derivatives with LiAlH4-AlCl3 was investigated in relation to the bulk of the C-3 substituens (H, OMe, OEt, OPr, OBzl).In ether-dichloromethane (2:1), 4
- Fuegedi, Peter,Liptak, Andras,Nanasi, Pal,Szejtli, Jozsef
-
-