176798-33-7Relevant articles and documents
Computer-aided engineering of a transglycosylase for the glucosylation of an unnatural disaccharide of relevance for bacterial antigen synthesis
Verges, Alize,Cambon, Emmanuelle,Barbe, Sophie,Salamone, Stphane,Le Guen, Yann,Moulis, Claire,Mulard, Laurence A.,Remaud-Simon, Magali,Andr, Isabelle
, p. 1186 - 1198 (2015)
The exploration of chemo-enzymatic routes to complex carbohydrates has been hampered by the lack of appropriate enzymatic tools having the substrate specificity for new reactions. Here, we used a computer-aided design framework to guide the construction of a small, diversity-controlled library of amino acid sequences of an α-transglucosylase, the sugar binding subsites of which were re-engineered to enable the challenging 1,2-cis-glucosylation of a partially protected β-linked disaccharide allyl (2-deoxy-2-trichloroacetamido-β-d-glucopyranosyl)-(1→2)-α-l-rhamnopyranoside, a potential intermediate in the synthesis of Shigella flexneri cell-surface oligosaccharides. The target disaccharide is not recognized by the parental wild-type enzyme and exhibits a molecular structure very distinct from that of the natural α-(1→4)-linked acceptor. A profound reshaping of the binding pocket had thus to be performed. Following the selection of 23 amino acid positions from the first shell, mutations were sampled using RosettaDesign leading to a subset of 1515 designed sequences, which were further analyzed by determining the amino acid variability among the designed sequences and their conservation in evolutionary-related enzymes. A combinatorial library of 2.7 × 104 variants was finally designed, constructed, and screened. One mutant showing the desired and totally new specificity was successfully identified from this first round of screening. Impressively, this mutant contained seven substitutions in the first shell of the active site leading to a drastic reshaping of the catalytic pocket without significantly perturbing the original specificity for sucrose donor substrate. This work illustrates how computer-aided approaches can undoubtedly offer novel opportunities to design tailored carbohydrate-active enzymes of interest for glycochemistry or synthetic glycobiology.
Total synthesis of the phenolic glycolipid mycoside B and the glycosylated p-hydroxybenzoic acid methyl ester HBAD-I, virulence markers of mycobacterium tuberculosis
Barroso, Santiago,Geerdink, Danny,Ter Horst, Bjorn,Casas-Arce, Eva,Minnaard, Adriaan J.
, p. 4642 - 4654 (2013/07/26)
The phenolic glycolipid mycoside B, present in Mycobacterium bovis and hypervirulent strains of Mycobacterium tuberculosis, has been synthesized for the first time. Multiple methyl groups were introduced by the extensive use of catalytic asymmetric 1,4-addition reactions, asymmetric hydrogenation of a β-keto ester afforded the basis for the central 1,3-diol moiety, and introduction of the 2-O-methyl-α-L-rhamnoside unit was achieved by stereoselective glycosylation with p-iodophenol and subsequent Sonogashira coupling, providing a basis for the generation of analogues. In addition, the related monosaccharide HBAD-I, present in the same species, has been efficiently synthesized for the first time by selective methylation of the hydroxy group at C-2 of a rhamnoside. The phenolic glycolipid mycoside B and the related phenolic glycoside HBAD-I from Mycobacterium tuberculosis have been synthesized for the first time. A highly convergent strategy was used featuring catalytic asymmetric 1,4-additions of MeMgBr and Me2Zn and a late-stage Sonogashira coupling as the key steps. Copyright
Dialkylation of various butane-2,3-diacetals using allylsilane and 1,8-bis(trimethylsilyl)-2,6-octadiene
Mariet, Natacha,Pellissier, Helene,Ibrahim-Ouali, Malika,Santelli, Maurice
, p. 2679 - 2691 (2007/10/03)
We report in this paper a greatly improved procedure for the formation of a range of 1-acetyl-1-methyl-2,5-divinylcyclopentanes from 1,8- bis(trimethylsilyl)octa-2,6-diene (BISTRO) and 1,2-diacetals prepared directly from biacetyl. These 1-acetyl-1-methyl
