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209 results on '"Gurcha, Sudagar S."'

1. Author Correction: The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth

Author

Franklin, Aaron, Salgueiro, Vivian C., Layton, Abigail J., Sullivan, Rudi, Mize, Todd, Vázquez-Iniesta, Lucía, Benedict, Samuel T., Gurcha, Sudagar S., Anso, Itxaso, Besra, Gurdyal S., Banzhaf, Manuel, Lovering, Andrew L., Williams, Spencer J., Guerin, Marcelo E., Scott, Nichollas E., Prados-Rosales, Rafael, Lowe, Elisabeth C., and Moynihan, Patrick J.

Published
2024
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2. The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth

Author

Franklin, Aaron, Salgueiro, Vivian C., Layton, Abigail J., Sullivan, Rudi, Mize, Todd, Vázquez-Iniesta, Lucía, Benedict, Samuel T., Gurcha, Sudagar S., Anso, Itxaso, Besra, Gurdyal S., Banzhaf, Manuel, Lovering, Andrew L., Williams, Spencer J., Guerin, Marcelo E., Scott, Nichollas E., Prados-Rosales, Rafael, Lowe, Elisabeth C., and Moynihan, Patrick J.

Published
2024
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6. The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth

Author

Franklin, Aaron, primary, Layton, Abigail J., additional, Mize, Todd, additional, Salgueiro, Vivian C., additional, Sullivan, Rudi, additional, Benedict, Samuel T., additional, Gurcha, Sudagar S., additional, Anso, Itxaso, additional, Besra, Gurdyal S., additional, Banzhaf, Manuel, additional, Lovering, Andrew L., additional, Williams, Spencer J., additional, Guerin, Marcelo E., additional, Scott, Nichollas E., additional, Prados-Rosales, Rafael, additional, Lowe, Elisabeth C., additional, and Moynihan, Patrick J., additional

Published
2023
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8. Structure of the priming arabinosyltransferase AftA required for AG biosynthesis of Mycobacterium tuberculosis.

Author

Yicheng Gong, Chuancun Wei, Jun Wang, Nengjiang Mu, Qinhong Lu, Chengyao Wu, Ning Yan, Huifang Yang, Yao Zhao, Xiuna Yang, Gurcha, Sudagar S., Veerapen, Natacha, Batt, Sarah M., Zhiqiang Hao, Lintai Da, Besra, Gurdyal S., Zihe Rao, and Lu Zhang

Subjects
MYCOBACTERIUM tuberculosis, TRANSMEMBRANE domains, BIOSYNTHESIS, DRUG discovery, ARABINOGALACTAN
Abstract

Arabinogalactan (AG) is an essential cell wall component in mycobacterial species, including the deadly human pathogen Mycobacterium tuberculosis. It plays a pivotal role in forming the rigid mycolyl-AG-peptidoglycan core for in vitro growth. AftA is a membrane-bound arabinosyltransferase and a key enzyme involved in AG biosynthesis which bridges the assembly of the arabinan chain to the galactan chain. It is known that AftA catalyzes the transfer of the first arabinofuranosyl residue from the donor decaprenyl-monophosphoryl-arabinose to the mature galactan chain (i.e., priming); however, the priming mechanism remains elusive. Herein, we report the cryo-EM structure of Mtb AftA. The detergent-embedded AftA assembles as a dimer with an interface maintained by both the transmembrane domain (TMD) and the soluble C-terminal domain (CTD) in the periplasm. The structure shows a conserved glycosyltransferase-C fold and two cavities converging at the active site. A metal ion participates in the interaction of TMD and CTD of each AftA molecule. Structural analyses combined with functional mutagenesis suggests a priming mechanism catalyzed by AftA in Mtb AG biosynthesis. Our data further provide a unique perspective into anti-TB drug discovery. [ABSTRACT FROM AUTHOR]

Published
2023
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13. Two polyketide-synthase-associated acyltransferases are required for sulfolipid biosynthesis in Mycobacterium tuberculosis

Author

Bhatt, Kiranmai, Gurcha, Sudagar S., Bhatt, Apoorva, Besra, Gurdyal S., and Jacobs, William R., Jr.

Subjects
Mycobacteria -- Genetic aspects, Mycobacteria -- Physiological aspects, Mycobacterium -- Genetic aspects, Mycobacterium -- Physiological aspects, Biological sciences
Abstract

The methyl-branched fatty acyl components of sulfolipid-I (SL-I), a major glycolipid of the human pathogen Mycobacterium tuberculosis, are synthesized by the polyketide synthase Pks2. Rv3824c (papA1), located downstream of pks2, encodes a protein that belongs to a subfamily of acyltransferases associated with mycobacterial polyketide synthases [polyketide synthase-associated proteins (PAPs)]. The presence of a conserved acyltransferase motif (H[X.sub.3]D[X.sub.14]Y) suggested a role for PapA1 in acylation of sulfated trehalose to form SL-I. Targeted deletion of the H37Rv papA1 resulted in loss of SL-I, demonstrating its role in mycobacterial sulfolipid biosynthesis. Furthermore, SL-I synthesis was restored in the mutant strain following complementation with papA1, but not with mutant alleles of papA1 containing alterations of key residues in the acyltransferase motif, confirming that PapA1 was an acyltransferase. While other M. tuberculosis pks clusters are associated with a single PAP-encoding gene, it was demonstrated that another open reading frame, Rv3820c (papA2), located 5.8 kb downstream of papA1 is also an acyltransferase gene involved in SL-I biosynthesis: deletion of papA2 abolished SL-I production. The absence of any partially acylated intermediates in either null mutant indicated that both PapA1 and PapA2 were required for all acylation steps of SL-I assembly.

Published
2007

14. The singular Corynebacterium glutamicum Emb arabinofuranosyltransferase polymerises the α(1 → 5) arabinan backbone in the early stages of cell wall arabinan biosynthesis

Author

Jankute, Monika, Alderwick, Luke J., Haslam, Stuart, Besra, Gurdyal S., Moorey, Alice R., Joe, Maju, Gurcha, Sudagar S., Eggeling, Lothar, Lowary, Todd L., Dell, Anne, Pang, Poh-Choo, and Yang, Tiandi

Subjects
Arabinogalactan, Cell envelope, lcsh:Cytology, ddc:570, Mycobacteria, Corynebacteria, lcsh:QH573-671, Article, Glycosyltransferase
Abstract

The arabinan-containing polysaccharides, arabinogalactan (AG) and lipoarabinomannan (LAM), are key cell wall components of the Corynebacterineae, which include Corynebacteria, Norcadia and Mycobacteria. Both AG and LAM contain elaborate arabinan domains composed of distinct structural motifs. Mycobacterial EmbA, EmbB and EmbC, collectively known as the Emb proteins, have been identified as arabinosyltransferases (ArafTs), which are targeted by the front-line anti-tubercular drug ethambutol. Previous studies have established that EmbA and EmbB play a role in the synthesis of the characteristic terminal hexa-arabinosuranosyl motif, whilst EmbC is involved exclusively in the biosynthesis of LAM. Herein, we have investigated the role of the singular Emb protein from Corynebacterium glutamicum through the detailed biochemical and chemical analysis of a double ΔaftAΔemb mutant, where the priming Cg-AftA protein, which generates the substrate for Cg-Emb has been deleted. Analysis of its cell wall revealed a complete absence of arabinose resulting in a truncated cell wall containing only a galactan backbone accompanied with complete loss of cell wall bound mycolates. In vitro cell-free assays using C. glutamicumΔaftA, C. glutamicumΔemb, C. glutamicumΔaftAΔemb and C. glutamicumΔaftBΔaftD and two synthetic acceptors, which mimick the arabinofuranose (Araf) “primed” galactan chain, demonstrated that Cg-Emb is able to transfer an Araf residue to the C5 of the Araf positioned on the synthetic acceptor(s). These results indicate that Cg-Emb acts as an α(1 → 5) ArafT and elongates the arabinan core during the early stages of arabinan biosynthesis in C. glutamicum. Keywords: Arabinogalactan, Cell envelope, Corynebacteria, Mycobacteria, Glycosyltransferase

Published
2018

16. Temperature-induced changes in the cell-wall components of Mycobacterium thermoresistibile

Author

Kremer, Laurent, Guerardel, Yann, Gurcha, Sudagar S., Locht, Camille, and Besra, Gurdyal S.

Subjects
Microbiological research -- Analysis, Bacterial cell walls -- Physiological aspects, Fatty acids -- Physiological aspects, Mycobacterium tuberculosis -- Physiological aspects, Mycobacterium tuberculosis -- Growth, Temperature -- Physiological aspects, Company growth, Biological sciences
Abstract

Research has been conducted on Mycobacterium thermoresistibile. The role of growth temperature in M. thermoresistibile complex lipid composition, mycolic and fatty acids has been investigated and the details are reported.

Published
2002

17. Azole antifungals are potent inhibitors of cytochrome P450 mono-oxygenases and bacterial growth in mycobacteria and streptomycetes

Author

McLean, Kirsty J., Marshall, Ker R., Richmond, Alison, Hunter, Iain S., Fowler, Kay, Kieser, Tobias, Gurcha, Sudagar S., Besra, Gurydal S., and Munro, Andrew W.

Subjects
Microbiological research -- Comparative analysis, Mycobacterium tuberculosis -- Physiological aspects, Mycobacterium tuberculosis -- Growth, Antibiotics -- Physiological aspects, Chemical inhibitors -- Physiological aspects, Growth factors -- Research, Streptomyces -- Physiological aspects, Company growth, Biological sciences
Abstract

Research has been conducted on Mycobacterium tuberculosis. The role of azole drugs in M. tuberculosis growth and their antibiotic effects have been investigated and the results indicate that these drugs are effective growth inhibitors of M. tuberculosis as well as of Streptomyces coelicolor and Streptomyces lividans.

Published
2002

18. Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol

Author

Zhang, Lu, primary, Zhao, Yao, additional, Gao, Yan, additional, Wu, Lijie, additional, Gao, Ruogu, additional, Zhang, Qi, additional, Wang, Yinan, additional, Wu, Chengyao, additional, Wu, Fangyu, additional, Gurcha, Sudagar S., additional, Veerapen, Natacha, additional, Batt, Sarah M., additional, Zhao, Wei, additional, Qin, Ling, additional, Yang, Xiuna, additional, Wang, Manfu, additional, Zhu, Yan, additional, Zhang, Bing, additional, Bi, Lijun, additional, Zhang, Xian’en, additional, Yang, Haitao, additional, Guddat, Luke W., additional, Xu, Wenqing, additional, Wang, Quan, additional, Li, Jun, additional, Besra, Gurdyal S., additional, and Rao, Zihe, additional

Published
2020
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19. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection

Author

Moody, D. Branch, Ulrichs, Timo, Muhlecker, Walter, Young, David C., Gurcha, Sudagar S., Grant, Ethan, Rosat, Jean-Pierre, Brenner, Michael B., Costello, Catherine E., Besra, Gurdyal S., and Porcelli, Steven A.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): D. Branch Moody (corresponding author) [1]; Timo Ulrichs [1, 2]; Walter Mühlecker [3]; David C. Young [3]; Sudagar S. Gurcha [4]; Ethan Grant [1]; Jean-Pierre Rosat [1]; Michael B. [...]

Published
2000
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27. Modular approach to triazole-linked 1,6-[alpha]-D-oligomannosides to the discovery of inhibitors of Mycobacterium tuberculosis cell wall synthetase

Author

Lo Conte, Mauro, Marra, Alberto, Chambery, Angela, Gurcha, Sudagar S., Besra, Gurdyal S., and Dondoni, Alessandro

Subjects
Ring formation (Chemistry) -- Analysis, Enzyme inhibitors -- Structure, Enzyme inhibitors -- Chemical properties, Transferases -- Structure, Transferases -- Chemical properties, Triazoles -- Structure, Triazoles -- Chemical properties, Biological sciences, Chemistry
Abstract

The inhibitors of mannosyltransferases are developed by preparing a range of triazole-linked 1,6-oligomannosides up to a hexadecamer by a modular approach centered on the Cu(I)-catalyzed azide-alkyne cycloaddition as key process. Suitable bioassays with dimer, tetramer, hexamer, octamer, decamer, and hexadecamer have displayed variable inhibitor activity against mycobacterial [alpha]-(1,6)-mannosyltransferases, the highest activity being registered with the hexamannoside and octamannoside.

Published
2010

28. Identification of KasA as the cellular target of an anti-tubercular scaffold

Author

Abrahams, Katherine A., Chung, Chun-Wa, Ghidelli-Disse, Sonja, Rullas, Joaquín, Rebollo-López, María José, Gurcha, Sudagar S., Cox, Jonathan A.G., Mendoza, Alfonso, Jiménez-Navarro, Elena, Martínez-Martínez, María Santos, Neu, Margarete, Shillings, Anthony, Homes, Paul, Argyrou, Argyrides, Casanueva, Ruth, Loman, Nicholas J., Moynihan, Patrick J., Lelièvre, Joël, Selenski, Carolyn, Axtman, Matthew, Kremer, Laurent, Bantscheff, Marcus, Angulo-Barturen, Iñigo, Izquierdo, Mónica Cacho, Cammack, Nicholas C., Drewes, Gerard, Ballell, Lluis, Barros, David, Besra, Gurdyal S., Bates, Robert H., Abrahams, Katherine A., Chung, Chun-Wa, Ghidelli-Disse, Sonja, Rullas, Joaquín, Rebollo-López, María José, Gurcha, Sudagar S., Cox, Jonathan A.G., Mendoza, Alfonso, Jiménez-Navarro, Elena, Martínez-Martínez, María Santos, Neu, Margarete, Shillings, Anthony, Homes, Paul, Argyrou, Argyrides, Casanueva, Ruth, Loman, Nicholas J., Moynihan, Patrick J., Lelièvre, Joël, Selenski, Carolyn, Axtman, Matthew, Kremer, Laurent, Bantscheff, Marcus, Angulo-Barturen, Iñigo, Izquierdo, Mónica Cacho, Cammack, Nicholas C., Drewes, Gerard, Ballell, Lluis, Barros, David, Besra, Gurdyal S., and Bates, Robert H.

Abstract

Phenotypic screens for bactericidal compounds are starting to yield promising hits against tuberculosis. In this regard, whole-genome sequencing of spontaneous resistant mutants generated against an indazole sulfonamide (GSK3011724A) identifies several specific single-nucleotide polymorphisms in the essential Mycobacterium tuberculosis β-ketoacyl synthase (kas) A gene. Here, this genomic-based target assignment is confirmed by biochemical assays, chemical proteomics and structural resolution of a KasA-GSK3011724A complex by X-ray crystallography. Finally, M. tuberculosis GSK3011724A-resistant mutants increase the in vitro minimum inhibitory concentration and the in vivo 99% effective dose in mice, establishing in vitro and in vivo target engagement. Surprisingly, the lack of target engagement of the related β-ketoacyl synthases (FabH and KasB) suggests a different mode of inhibition when compared with other Kas inhibitors of fatty acid biosynthesis in bacteria. These results clearly identify KasA as the biological target of GSK3011724A and validate this enzyme for further drug discovery efforts against tuberculosis.

Published
2016

29. THPP target assignment reveals EchA6 as an essential fatty acid shuttle in mycobacteria

Author

Cox, Jonathan A.G., Abrahams, Katherine A., Alemparte, Carlos, Ghidelli-Disse, Sonja, Rullas, Joaquín, Angulo-Barturen, Iñigo, Singh, Albel, Gurcha, Sudagar S., Nataraj, Vijayashankar, Bethell, Stephen, Remuiñán, Modesto J., Encinas, Lourdes, Jervis, Peter J., Cammack, Nicholas C., Bhatt, Apoorva, Kruse, Ulrich, Bantscheff, Marcus, Fütterer, Klaus, Barros, David, Ballell, Lluis, Drewes, Gerard, Besra, Gurdyal S., Cox, Jonathan A.G., Abrahams, Katherine A., Alemparte, Carlos, Ghidelli-Disse, Sonja, Rullas, Joaquín, Angulo-Barturen, Iñigo, Singh, Albel, Gurcha, Sudagar S., Nataraj, Vijayashankar, Bethell, Stephen, Remuiñán, Modesto J., Encinas, Lourdes, Jervis, Peter J., Cammack, Nicholas C., Bhatt, Apoorva, Kruse, Ulrich, Bantscheff, Marcus, Fütterer, Klaus, Barros, David, Ballell, Lluis, Drewes, Gerard, and Besra, Gurdyal S.

Abstract

Phenotypic screens for bactericidal compounds against drug-resistant tuberculosis are beginning to yield novel inhibitors. However, reliable target identification remains challenging. Here, we show that tetrahydropyrazo[1,5-a]pyrimidine-3-carboxamide (THPP) selectively pulls down EchA6 in a stereospecific manner, instead of the previously assigned target Mycobacterium tuberculosis MmpL3. While homologous to mammalian enoyl-coenzyme A (CoA) hydratases, EchA6 is non-catalytic yet essential and binds long-chain acyl-CoAs. THPP inhibitors compete with CoA-binding, suppress mycolic acid synthesis, and are bactericidal in a mouse model of chronic tuberculosis infection. A point mutation, W133A, abrogated THPP-binding and increased both the in vitro minimum inhibitory concentration and the in vivo effective dose 99 in mice. Surprisingly, EchA6 interacts with selected enzymes of fatty acid synthase II (FAS-II) in bacterial two-hybrid assays, suggesting essentiality may be linked to feeding long-chain fatty acids to FAS-II. Finally, our data show that spontaneous resistance-conferring mutations can potentially obscure the actual target or alternative targets of small molecule inhibitors.

Published
2016

30. Identification of KasA as the cellular target of an anti-tubercular scaffold

Author

Abrahams, Katherine A., primary, Chung, Chun-wa, additional, Ghidelli-Disse, Sonja, additional, Rullas, Joaquín, additional, Rebollo-López, María José, additional, Gurcha, Sudagar S., additional, Cox, Jonathan A. G., additional, Mendoza, Alfonso, additional, Jiménez-Navarro, Elena, additional, Martínez-Martínez, María Santos, additional, Neu, Margarete, additional, Shillings, Anthony, additional, Homes, Paul, additional, Argyrou, Argyrides, additional, Casanueva, Ruth, additional, Loman, Nicholas J., additional, Moynihan, Patrick J., additional, Lelièvre, Joël, additional, Selenski, Carolyn, additional, Axtman, Matthew, additional, Kremer, Laurent, additional, Bantscheff, Marcus, additional, Angulo-Barturen, Iñigo, additional, Izquierdo, Mónica Cacho, additional, Cammack, Nicholas C., additional, Drewes, Gerard, additional, Ballell, Lluis, additional, Barros, David, additional, Besra, Gurdyal S., additional, and Bates, Robert H., additional

Published
2016
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31. THPP target assignment reveals EchA6 as an essential fatty acid shuttle in mycobacteria

Author

Cox, Jonathan A. G., primary, Abrahams, Katherine A., additional, Alemparte, Carlos, additional, Ghidelli-Disse, Sonja, additional, Rullas, Joaquín, additional, Angulo-Barturen, Iñigo, additional, Singh, Albel, additional, Gurcha, Sudagar S., additional, Nataraj, Vijayashankar, additional, Bethell, Stephen, additional, Remuiñán, Modesto J., additional, Encinas, Lourdes, additional, Jervis, Peter J., additional, Cammack, Nicholas C., additional, Bhatt, Apoorva, additional, Kruse, Ulrich, additional, Bantscheff, Marcus, additional, Fütterer, Klaus, additional, Barros, David, additional, Ballell, Lluis, additional, Drewes, Gerard, additional, and Besra, Gurdyal S., additional

Published
2016
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32. Biochemical and Structural Characterization of Mycobacterial Aspartyl-tRNA Synthetase AspS, a Promising TB Drug Target

Author

Gurcha, Sudagar S., primary, Usha, Veeraraghavan, additional, Cox, Jonathan A. G., additional, Fütterer, Klaus, additional, Abrahams, Katherine A., additional, Bhatt, Apoorva, additional, Alderwick, Luke J., additional, Reynolds, Robert C., additional, Loman, Nicholas J., additional, Nataraj, VijayaShankar, additional, Alemparte, Carlos, additional, Barros, David, additional, Lloyd, Adrian J., additional, Ballell, Lluis, additional, Hobrath, Judith V., additional, and Besra, Gurdyal S., additional

Published
2014
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33. Selectfluor and NFSI exo‐Glycal Fluorination Strategies Applied to the Enhancement of the Binding Affinity of Galactofuranosyltransferase GlfT2 Inhibitors

Author

Dumitrescu, Lidia, primary, Eppe, Guillaume, additional, Tikad, Abdellatif, additional, Pan, Weidong, additional, Bkassiny, Sandy El, additional, Gurcha, Sudagar S., additional, Ardá, Ana, additional, Jiménez‐Barbero, Jesús, additional, Besra, Gurdyal S., additional, and Vincent, Stéphane P., additional

Published
2014
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34. Characterization of a putative alpha-mannosyltransferase involved in phosphatidylinositol trimannoside biosynthesis in Mycobacterium tuberculosis

Author

Kremer, Laurent, Gurcha, Sudagar S, Bifani, Pablo, Hitchen, Paul G, Baulard, Alain, Morris, Howard R, Dell, Anne, Brennan, Patrick J, and Besra, Gurdyal S

Subjects
DNA, Bacterial, Guanosine Diphosphate Mannose, Lipopolysaccharides, Molecular Sequence Data, Mycobacterium smegmatis, Mycobacterium tuberculosis, Spectrometry, Mass, Fast Atom Bombardment, Phosphatidylinositols, Mannosyltransferases, Mycobacterium bovis, Bacterial Proteins, hemic and lymphatic diseases, Amino Acid Sequence, Sequence Alignment, Research Article
Abstract

Phosphatidyl-myo-inositol mannosides (PIMs), lipomannan (LM) and lipoarabinomannan (LAM) are an important class of bacterial factors termed modulins that are found in tuberculosis and leprosy. Although their structures are well established, little is known with respect to the molecular aspects of the biosynthetic machinery involved in the synthesis of these glycolipids. On the basis of sequence similarity to other glycosyltransferases and our previous studies defining an alpha-mannosyltransferase from Mycobacterium tuberculosis, named PimB [Schaeffer, Khoo, Besra, Chatterjee, Brennan, Belisle and Inamine (1999) J. Biol. Chem. 274, 31625-31631], which catalysed the formation of triacyl (Ac(3))-PIM(2) (i.e. the dimannoside), we have identified a related gene from M. tuberculosis CDC1551, now designated pimC. The use of a cell-free assay containing GDP-[(14)C]mannose, amphomycin and membranes from Myobacterium smegmatis overexpressing PimC led to the synthesis of a new alkali-labile PIM product. Fast-atom-bombardment MS established the identity of the new enzymically synthesized product as Ac(3)PIM(3) (i.e. the trimannoside). The results indicate that pimC encodes an alpha-mannosyltransferase involved in Ac(3)PIM(3) biosynthesis. However, inactivation of pimC in Myobacterium bovis Bacille Calmette-Guérin (BCG) did not affect the production of higher PIMs, LM and LAM when compared with wild-type M. bovis BCG, suggesting the existence of redundant gene(s) or an alternate pathway that may compensate for this PimC deficiency. Further analyses, which compared the distribution of pimC in a panel of M. tuberculosis strains, revealed that pimC was present in only 22% of the clinical isolates examined.

Published
2002

36. Cord Factor and Peptidoglycan Recapitulate the Th17-Promoting Adjuvant Activity of Mycobacteria through Mincle/CARD9 Signaling and the Inflammasome

Author

Shenderov, Kevin, primary, Barber, Daniel L., additional, Mayer-Barber, Katrin D., additional, Gurcha, Sudagar S., additional, Jankovic, Dragana, additional, Feng, Carl G., additional, Oland, Sandy, additional, Hieny, Sara, additional, Caspar, Pat, additional, Yamasaki, Sho, additional, Lin, Xin, additional, Ting, Jenny P. -Y., additional, Trinchieri, Giorgio, additional, Besra, Gurdyal S., additional, Cerundolo, Vincenzo, additional, and Sher, Alan, additional

Published
2013
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39. Zebrafish embryo screen for mycobacterial genes involved in the initiation of granuloma formation reveals a newly identified ESX-1 component

Author

Stoop, Esther J. M., primary, Schipper, Tim, additional, Rosendahl Huber, Sietske K., additional, Nezhinsky, Alexander E., additional, Verbeek, Fons J., additional, Gurcha, Sudagar S., additional, Besra, Gurdyal S., additional, Vandenbroucke-Grauls, Christina M. J. E., additional, Bitter, Wilbert, additional, and van der Sar, Astrid M., additional

Published
2011
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44. Role of Phosphatidylinositol Mannosides in the Interaction between Mycobacteria and DC-SIGN

Author

Driessen, Nicole N., primary, Ummels, Roy, additional, Maaskant, Janneke J., additional, Gurcha, Sudagar S., additional, Besra, Gurdyal S., additional, Ainge, Gary D., additional, Larsen, David S., additional, Painter, Gavin F., additional, Vandenbroucke-Grauls, Christina M. J. E., additional, Geurtsen, Jeroen, additional, and Appelmelk, Ben J., additional

Published
2009
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48. Expression, purification and characterisation of soluble GlfT and the identification of a novel galactofuranosyltransferase Rv3782 involved in priming GlfT-mediated galactan polymerisation in Mycobacterium tuberculosis

Author

Alderwick, Luke J., primary, Dover, Lynn G., additional, Veerapen, Natacha, additional, Gurcha, Sudagar S., additional, Kremer, Laurent, additional, Roper, David L., additional, Pathak, Ashish K., additional, Reynolds, Robert C., additional, and Besra, Gurdyal S., additional

Published
2008
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50. Selectfluor and NFSI exo-Glycal Fluorination Strategies Applied to the Enhancement of the Binding Affinity of Galactofuranosyltransferase Gl fT2 Inhibitors.

Author

Dumitrescu, Lidia, Eppe, Guillaume, Tikad, Abdellatif, Pan, Weidong, Bkassiny, Sandy El, Gurcha, Sudagar S., Ardá, Ana, Jiménez ‐ Barbero, Jesús, Besra, Gurdyal S., and Vincent, Stéphane P.

Subjects
GLYCALS, FLUORINATION, CHEMICAL synthesis, FURANOSIDES, PYRANOSIDE, FLUORINE
Abstract

Two complementary methods for the synthesis of fluorinated exo-glycals have been developed, for which previously no general reaction had been available. First, a Selectfluor-mediated fluorination was optimized after detailed analysis of all the reaction parameters. A dramatic effect of molecular sieves on the course of the reaction was observed. The reaction was generalized with a set of biologically relevant furanosides and pyranosides. A second direct approach involving carbanionic chemistry and the use of N-fluorobenzenesulfonimide (NFSI) was performed and this method gave better diastereoselectivities. Assignment of the Z/ E configuration of all the fluorinated exo-glycals was achieved based on the results of HOESY experiments. Furthermore, fluorinated exo-glycal analogues of UDP-galactofuranose were prepared and assayed against Gl fT2, which is a key enzyme involved in the cell-wall biosynthesis of major pathogens. The fluorinated exo-glycals proved to be potent inhibitors as compared with a series of C-glycosidic analogues of UDP-Gal f, thus demonstrating the double beneficial effect of the exocyclic enol ether functionality and the fluorine atom. [ABSTRACT FROM AUTHOR]

Published
2014
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