- Synthesis and structure reassignment of malylglutamate, a recently discovered earthworm metabolite
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Malylglutamate, a newly identified metabolite in earthworms, was synthesized using a traditional peptide coupling approach for assembling the amide from protected malate and glutamate precursors. The proposed structure (1) and a diastereomer were synthesized, but their NMR spectra did not match the natural sample. Further analysis of the natural sample using HMBC spectroscopy suggested an alternative attachment of the malyl moiety, and β-malylglutamate (2) diastereomers were synthesized, L,L-2 and D,D-2. NMR spectra were an excellent match with the natural sample, and chiral-phase chromatography was employed to identify (a)-β-l-malyl-l-glutamate (2) as the isomer native to Eisenia fetida.
- Griffith, Corey M.,Feceu, Abigail,Larive, Cynthia K.,Martin, David B. C.
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p. 417 - 421
(2019/02/19)
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- Inhibitors for bacterial cell-wall recycling
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Gram-negative bacteria have evolved an elaborate process for the recycling of their cell wall, which is initiated in the periplasmic space by the action of lytic transglycosylases. The product of this reaction, β-d-N- acetylglucosamine-(1a?'4)-1,6-anhydro-β-d-N-acetylmuramyl-l- Ala-I-d-Glu-meso-DAP-d-Ala-d-Ala (compound 1), is internalized to begin the recycling events within the cytoplasm. The first step in the cytoplasmic recycling is catalyzed by the NagZ glycosylase, which cleaves in a hydrolytic reaction the N-acetylglucosamine glycosidic bond of metabolite 1. The reactions catalyzed by both the lytic glycosylases and NagZ are believed to involve oxocarbenium transition species. We describe herein the synthesis and evaluation of four iminosaccharides as possible mimetics of the oxocarbenium species, and we disclose one as a potent (compound 3, Ki = 300 A± 15 nM) competitive inhibitor of NagZ.
- Yamaguchi, Takao,Blazquez, Blas,Hesek, Dusan,Lee, Mijoon,Llarrull, Leticia I.,Boggess, Bill,Oliver, Allen G.,Fisher, Jed F.,Mobashery, Shahriar
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supporting information; experimental part
p. 238 - 242
(2012/05/04)
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- Tryptophan-containing dipeptide derivatives as potent PPARγ antagonists: Design, synthesis, biological evaluation, and molecular modeling
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The discovery of peroxisome proliferator-activated receptor γ (PPARγ) antagonists (also termed "selective PPARγ modulators, SPPARγM") is now of a great interest in the treatment of diabetes and obesity. The structure of compound 1a (G3335, Fig. 1), a novel class of PPARγ antagonist, is entirely different from that of other reported PPARγ antagonists. A series of 35 novel analogues (1b-l, 9a-d, 13a-t) were designed, synthesized and evaluated against the agonistic effects exerted by rosiglitazone. These results indicated that most functional groups of 1a were conserved, and six new compounds (1b, 1c, and 9a-d) exhibited strong PPARγ antagonistic activities (IC50 values of 5.2-25.8 μM) against 10 μM rosiglitazone in the promotion of the PPARγ-LBD-CBP (ligand-binding domain and cAMP-response-element binding protein) interaction as investigated by yeast two-hybrid technology based assay. Molecular modeling studies for compounds 1a-d, 1h, 9c-d, and 13a were also presented.
- Deng, Guanghui,Liu, Zhiguo,Ye, Fei,Luo, Xiaomin,Zhu, Weiliang,Shen, Xu,Liu, Hong,Jiang, Hualiang
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experimental part
p. 2699 - 2716
(2009/04/11)
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