- Toward the development of prophylactic and therapeutic human papillomavirus type-16 lipopeptide vaccines
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Four lipid-core peptide systems were synthesized using stepwise solid-phase peptide synthesis, incorporating a sequence from the human papillomavirus type-16 (HPV-16) E7 protein (E744-62), for the purpose of developing vaccines against HPV-16 associated cervical cancer. D-Mannose was conjugated to the vaccine in order to investigate whether the targeting of dendritic cell mannose receptors would improve vaccine efficacy. The ability of the vaccines to clear or reduce the size of HPV-16 associated tumors was assessed in C57BL/6 (H-2b) mice using the TC-1 HPV-16 tumor model. Overall, significant reductions in the size of TC-1 tumors were observed in the mouse model, with the conjugation of mannose to these vaccines demonstrated to clear or reduce the size of TC-1 tumors to a greater extent than non-mannose-containing vaccines (37 out of 40 versus 21 out of 30 tumors cleared, respectively).
- Moyle, Peter M.,Olive, Colleen,Ho, Mei-Fong,Pandey, Manisha,Dyer, Joanne,Suhrbier, Andreas,Fujita, Yoshio,Toth, Istvan
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Read Online
- Synthesis of podophyllotoxin-glycosyl triazoles via click protocol mediated by silver (I)-N-heterocyclic carbenes and their anticancer evaluation as topoisomerase-II inhibitors
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Herein we report the regioselective synthesis of podophyllotoxin-Glycosyl triazole hybrids catalysed by Ag(I)-N-heterocyclic carbene (Ag(I)-NHC) in a short reaction time (~30 min) at ambient conditions. In principle, it is the first report of Click alkyne-azide cycloaddition catalysed by Ag(I)-NHC catalyst and moreover, this new methodology yielded good results when compared with traditional CuAAC in terms of reaction time and selectivity. The synthesised compounds were further explored for in vitro anticancer activity against four human cancer cell lines Du145, HeLa, A-549, and MCF-7 and found that these synthesised compounds possess significant anticancer activity. Further, the compounds 5a and 5e were identified as promising leads due to their better activity across all cell lines than that of the standard drug etoposide. Molecular docking studies of 5a & 5e with DNA Topoisomerase-II were revealed that the free energy calculations of active compounds were in good agreement with observed IC50 values.
- Nerella, Srinivas,Kankala, Shravankumar,Gavaji, Brahmeshwari
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- CuAAC mediated synthesis of cyclen cored glycodendrimers of high sugar tethers at low generation
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Glycodendrimers are receiving considerable attention to mimic a number of imperative features of cell surface glycoconjugate and acquired excellent relevance to a wide domain of investigations including medicine, pharmaceutics, catalysis, nanotechnology, carbohydrate-protein interaction, and moreover in drug delivery systems. Toward this end, an expeditious, modular, and regioselective triazole-forming CuAAC click approach along with double stage convergent synthetic method was chosen to develop a variety of novel chlorine-containing cyclen cored glycodendrimers of high sugar tethers at low generation of promising therapeutic potential. We developed a novel chlorine-containing hypercore unit with 12 alkynyl functionality originated from cyclen scaffold which was confirmed by its single crystal X-ray data analysis. Further, the modular CuAAC technique was utilized to produce a variety of novel 12–sugar coated (G0) glycodendrimers 12-15 adorn with β-Glc-, β-Man-, β-Gal-, β-Lac, along with 36-galactose coated (G1) glycodendrimer 18 in good-to-high yield. The structures of the developed glycodendrimer architectures have been well elucidated by extensive spectral analysis including NMR (1H & 13CNMR), HRMS, MALDI-TOF MS, UV–Vis, IR, and SEC (Size Exclusion Chromatogram) data.
- Agrahari, Anand K.,Jaiswal, Manoj K.,Yadav, Mangal S.,Tiwari, Vinod K.
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- Design, synthesis and biological evaluation of carbohydrate-based sulphonamide derivatives as topical antiglaucoma agents through selective inhibition of carbonic anhydrase II
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A series of new carbohydrate-based sulphonamide derivatives were designed, synthesised by employing the so-call ‘sugar-tail’ approach. The compounds were evaluated in vitro against a panel of CAs. Compared to their parent compound p-sulfamoylbenzoic acid, these compounds showed nearly 100-fold improvement in their binding affinities against hCA II in vitro. All of compounds showed great water solubility and the pH value of their water solutions of compounds is 7.0. Such properties are advantageous to make them much less irritating to the eye when applied topical glaucomatous drugs, compared to the relatively highly acidic dorzolamide preparations (pH 5.5). Notably, compounds 7d, 7 g, 7 h demonstrated to topically lower intraocular pressure (IOP) in glaucomatous animals better than brinzolamide when applied as a 1% solution directly into the eye. Low cytotoxicity on human cornea epithelial cell was observed in the tested concentrations by the MTT assay.
- Fan, Zhanfang,Guo, Chun,Hou, Zhuang,Li, Chuanchao,Lin, Bin,Liu, Yang,Liu, Yichuang,Wang, Yitong,Zhang, Miao
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p. 383 - 390
(2019/12/30)
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- Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations
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For investigations on the biological functions of oligosaccharides and peptidomimetics, new asparagine-based mono- and disaccharides containing glycopeptides were prepared in solution. The applicability of two common peptide coupling reagents, using an or
- Sr?an, Laura,Ziegler, Thomas
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supporting information
p. 888 - 894
(2020/05/18)
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- Glycoprotein Mimics with Tunable Functionalization through Global Amino Acid Substitution and Copper Click Chemistry
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Glycoproteins and their mimics are challenging to produce because of their large number of polysaccharide side chains that form a densely grafted protein-polysaccharide brush architecture. Herein a new approach to protein bioconjugate synthesis is demonst
- Seifried, Brian M.,Qi, Wenjing,Yang, Yun Jung,Mai, Danielle J.,Puryear, Wendy B.,Runstadler, Jonathan A.,Chen, Guosong,Olsen, Bradley D.
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p. 554 - 566
(2020/03/04)
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- Novel carbohydrate modified berberine derivatives: Synthesis and: In vitro anti-diabetic investigation
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Berberine is a bioactive alkaloid used in Chinese medicine and has numerous positive effects on biological systems. This paper describes the facile and highly efficient synthesis of some carbohydrate modified berberine derivatives, and conjugation of the carbohydrate moiety with berberine was finished by "click" chemistry. The cytotoxicity and anti-diabetic measurements of all berberine derivatives were accomplished on HepG2 cell lines, and the results indicated that most of the derivatives exhibit higher anti-diabetic activity than berberine. The mannose modified berberine derivative has significantly lower cytotoxicity than berberine, and the induced IC50 value of this derivative is nearly 1.5 times that of berberine. Furthermore, this mannose modified berberine derivative exhibits high anti-diabetic activity at both high and low drug concentrations, thereby indicating its potential application for the development of novel anti-diabetic drugs.
- Han, Liwen,Sheng, Wenlong,Li, Xiaobin,Sik, Attila,Lin, Houwen,Liu, Kechun,Wang, Lizhen
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p. 598 - 605
(2019/04/30)
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- Synthesis, Characterization, X-Ray Crystallography, and Antileishmanial Activities of N-Linked and O-Linked Glycopyranosides
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Novel N-linked 5a-e and O-linked glycopyranosides 7a-e were synthesized in high yield from commercially available L-tartaric acid containing two asymmetric centers and C2 axis of symmetry. The compound L-tartaric acid was completely protected and then partially hydrolyzed to get the monoester, which upon treatment with different amino and hydroxyl derivatives of glycopyranoses gave the desired amides and esters. The synthesized derivatives were purified by chromatography and characterized by spectroanalytical techniques. The structure of compound 7c in the series was supported by X-ray analysis. Leishmanicidal activities of compounds 5a-e and 7a-e were investigated which showed moderate to good activities.
- Rashid, Haroon Ur,Khan, Sher Wali,Khan, Momin,Nadhman, Akhtar,Rehman, Noor,Tariq, Muhammad,Yousuf, Sammer
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- Synthesis and anti-cancer activities of new sulfonamides 4-substituted-triazolyl nucleosides
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Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell lines, AICAR is under clinical development for several pathologies, thanks to its original mode of action. Indeed, AICAR induced autophagy cell death and is able, following this mechanism, to circumvent resistance to apoptotic drugs including kinase inhibitors currently on the market. To improve the activity of AICAR, we report herein an efficient synthesis of new series of sulfonamide-4-substituted-1,2,3-triazolyl nucleosides using a Cu-catalyzed 1,3-dipolar cycloaddition. All these molecules have been fully characterized and evaluated against two aggressive tumor cell lines, RCC4 and MDA-MB-231. Among them, nucleoside analogue 5i belonging to the ribose series was found to be 19 to 66-fold more active than AICAR. Western blot analyses on RCC4 cells showed that 5i displayed an interesting mode of action by inducing both apoptosis and autophagy cell death, making therefore this class of molecules highly promising for further hit-to-lead optimization.
- Alaoui, Soukaina,Dufies, Maeva,Driowya, Mohsine,Demange, Luc,Bougrin, Khalid,Robert, Guillaume,Auberger, Patrick,Pagès, Gilles,Benhida, Rachid
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supporting information
p. 1989 - 1992
(2017/04/10)
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- Exploring the effect of bioisosteric replacement of carboxamide by a sulfonamide moiety on N-glycosidic torsions and molecular assembly: Synthesis and x-ray crystallographic investigation of n-(β- D -glycosyl)sulfonamides as n-glycoprotein linkage region analogues
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N-Glycoprotein linkage region constituents, 2-acetamido-2-deoxy-β-D- glucopyranose (GlcNAc) and asparagine (Asn) are conserved among all the eukaryotes. To gain a better understanding for nature's choice of GlcNAcβAsn as linkage region constituents and inter- and intramolecular carbohydrate-protein interactions, a detailed systemic structural study of the linkage region conformation is essential. Earlier crystallographic studies of several N-(β-glycopyranosyl)alkanamides showed that N-glycosidic torsion, φN, is influenced to a larger extent by structural variation in the sugar part than that of the aglycon moiety. To explore the effect of the bioisosteric replacement of a carboxamide group by a sulfonamide moiety on the N-glycosidic torsions as well as on molecular assembly, several glycosyl methanesulfonamides and glycosyl chloromethanesulfonamides were synthesized as analogues of the N-glycoprotein linkage region, and crystal structures of seven of these compounds have been solved. A comparative analysis of this series of crystal structures as well as with those of the corresponding alkanamido derivatives revealed that N-glycosidic torsion, φN, does not alter significantly. Methanesulfonamido and chloromethanesulfonamido derivatives of GlcNAc display a different aglycon conformation compared to other sulfonamido analogues. This may be due to the cumulative effect of the direct hydrogen bonding between N1 and O1′ and C-H×××O interactions of the aglycon chain, revealing the uniqueness of the GlcNAc as the linkage sugar. Unique molecular assembly motif of GlcNAc: The different aglycon conformations of methanesulfonamido and chloromethanesulfonamido derivatives of GlcNAc as compared to other sulfonamido analogues is a unique feature of their molecular assembly. This could be due to the cumulative effect of the direct hydrogen bonding between N1 and O1′ and C-H×××O interactions of the aglycon chain. Copyright
- Srivastava, Amrita,Varghese, Babu,Loganathan, Duraikkannu
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p. 17720 - 17732
(2014/01/17)
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- Regiospecific anomerisation of acylated glycosyl azides and benzoylated disaccharides by using TiCl4
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Chelation induced anomerisation is promoted when Lewis acids, such as TiCl4 or SnCl4, coordinate to the pyranose ring oxygen atom and another site, giving rise to endocyclic cleavage and isomerisation to the more stable anomer. In this research regiospecific site-directed anomerisation is demonstrated. TiCl4 (2.5equiv) was employed to induce anomerisation of 15 glycosyl azide and disaccharide substrates of low reactivity, and high yields (>75 %) and stereoselectivies (α/β>9:1) were achieved. The examples included glucopyranuronate, galactopyranuronate and mannopyranuronate as well as N-acetylated glucopyranuronate and galactopyranuronate derivatives. A disaccharide with the α1→4 linkage found in polygalacturonan was included. The use of benzoylated saccharides was found to be important in disaccharide anomerisation as attempts to isomerise related acetyl protected and 2,3-carbonate protected derivatives were not successful. Copyright
- Farrell, Mark,Zhou, Jian,Murphy, Paul V.
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p. 14836 - 14851
(2013/11/06)
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- Expedient and facile one-pot syntheses of triazole-linked glycoconjugates under microwave irradiation
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Effective microwave assisted one-pot syntheses of triazole-O- glycoconjugates and triazolylglycosides involving sequential glycosylation and click chemistry are described. Georg Thieme Verlag Stuttgart · New York.
- Sarkar, Swarbhanu,Dutta, Samrat,Sen, Asish Kumar
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experimental part
p. 1079 - 1089
(2012/05/20)
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- A new pH-switchable dimannosyl[c2]daisy chain molecular machine
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(Figure Presented) The preparation of a dimannosyl[c2]daisy chain molecular machine containing an ammonium and a triazolium station is described. The both stretched and contracted states of the molecular machine can be obtained by variation of the pH, thus localizing the mannosyl stoppers closer or farther away.
- Coutrot, Frederic,Romuald, Camille,Busseron, Eric
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supporting information; experimental part
p. 3741 - 3744
(2009/07/09)
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- Determination of the anomeric configurations of 2,3,4,6-tetra-o-acetyl-D- mannopyranosyl azide
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The structures of 2,3,4,6-tetra-O-acetyl-?-d-mannopyranosyl azide and 2,3,4,6-tetra-O-acetyl-?-d-mannopyranosyl azide were determined using X-ray crystallographic and one-dimensional NOESY techniques. CSIRO 2006.
- Cosgrove, Kelly L.,Bernhardt, Paul V.,Ross, Benjamin P.,McGeary, Ross P.
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p. 473 - 476
(2007/10/03)
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- General methods for the synthesis of glycopyranosyluronic acid azides
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Per-O-acetylated D-glycopyranoses derived from both mono- and disaccharides were first converted to glycosyl iodides and subsequently reacted with an azide source to achieve the stereoselective synthesis of β-D-glycosyl azides after deacetylation. Low-temperature (4°C) TEMPO oxidation of the monosaccharides provided the corresponding uronic acids, which were purified as the free acids. Oxidation of the lactosyl- and cellobiosyl azides resulted in diacid formation. However, 4′,6′-O-benzylidene protection enabled selective oxidation of the C-6 hydroxyl. 2-Acetamido-2-deoxy-D-glycopyranosyl azides were also prepared and converted to uronic acids completing the library synthesis.
- Ying, Laiqiang,Gervay-Hague, Jacquelyn
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p. 835 - 841
(2007/10/03)
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- Synthesis and activity of dipeptides, linked to targeting ligands, as specific NK cell enhancers
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Water soluble analogues of the lipophilic immunostimulant, octadecyl D- alanyl-L-glutamine, BCH-527, were synthesized and evaluated for the ability to stimulate natural killer (NK) cells. One of these compounds in which the octadecyl chain of BCH-527 was
- Abbott, Shaun D.,Gagnon, Lyne,Lagraoui, Mouna,Kadhim, Salam,Attardo, Giorgio,Zacharie, Boulos,Penney, Christopher L.
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p. 1909 - 1926
(2007/10/03)
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