共查询到20条相似文献,搜索用时 31 毫秒
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Sorangiadenosine (1), a novel nucleoside possessing a bicyclic, eudesmane-type sesquiterpene as an auxiliary component, was isolated from the culture broth of the gliding bacterium Sorangium cellulosum KM1003, collected from Korean soil. The chemical structure of this compound was determined by combined spectroscopic and chemical analyses. The new compound exhibited moderate antibacterial activity against a wide range of bacterial strains. 相似文献
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Streptolydigin is a highly potent, broad-spectrum antibiotic produced by Streptomyces lydicus, which inhibits bacterial RNA polymerase. We describe the first synthesis of streptolydigin, which was assembled in a highly convergent and fully stereocontrolled fashion with a longest linear sequence of 24 steps starting from commercially available precursors. The assembly process entailed preparation of fully elaborated streptolic and ydiginic subunits of the natural product, followed by a highly efficient union in a three-step one-pot procedure, which included Dieckmann cyclization with a concomitant imide opening, Horner-Wadsworth-Emmons olefination, and desilylation. 相似文献
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[structure: see text] The relative and absolute stereochemistry of the structurally unique 24-membered myxobacterial macrolides archazolid A and B, highly potent vacuolar-type ATPase (V-ATPase) inhibitors in vitro and in vivo, was determined on the basis of a combination of extensive high-field NMR studies, including J-based configuration analysis, molecular modeling, and chemical methods. 相似文献
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Mitsunobu Doi Toshimasa Ishida Yoshio Katsuya Masahiro Sasaki Taizo Taniguchi Hiroshi Hasegawa Tsutomu Mimoto Yoshiaki Kiso 《Acta Crystallographica. Section C, Structural Chemistry》2001,57(11):1333-1335
Kynostatin {KNI-272; systematic name: 3-[3-benzyl-2-hydroxy-9-(isoquinolin-5-yloxy)-6-methylsulfanylmethyl-5,8-dioxo-4,7-diazanonanoyl]-N-tert-butyl-1,3-thiazolane-4-carboxamide}, a highly selective and potent HIV protease inhibitor containing allophenylnorstatin [(2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid], has been crystallized as the hydrate, C33H41N5O6S2·0.803H2O, from aqueous hexylene glycol. The observed disorder of the phenyl group in the structure is related to the mode of hydration. The backbone conformation of the molecule is twisted and the overall conformation of the free inhibitor is similar to that observed in its complex with HIV protease. 相似文献
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Plaza A Garcia R Bifulco G Martinez JP Hüttel S Sasse F Meyerhans A Stadler M Müller R 《Organic letters》2012,14(11):2854-2857
Aetheramides are structurally distinctive cyclic peptides isolated from a novel myxobacterial genus proposed to be termed "Aetherobacter". The structures were solved by a combination of NMR analyses, quantum mechanical calculations, and chemical derivatizations. Aetheramides which contain a unique polyketide moiety and two amino acid residues potently inhibited HIV-1 infection with IC(50) values of ~0.015 μM. Furthermore aetheramides showed cytostatic activity against human colon carcinoma (HCT-116) cells with IC(50) values of 0.11 μM. 相似文献
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Frank B Knauber J Steinmetz H Scharfe M Blöcker H Beyer S Müller R 《Chemistry & biology》2007,14(2):221-233
Natural products constitute important lead structures in drug discovery. In bacteria, they are often synthesized by large, modular multienzyme complexes. Detailed analysis of the biosynthetic machinery should enable its directed engineering and production of desirable analogs. The myxobacterium Sorangium cellulosum So ce90 produces the cytotoxic spiroketal polyketide spirangien, for which we describe the identification and functional analysis of the biosynthetic pathway. The gene cluster spans 88 kb and encodes 7 type I polyketide synthases and additional enzymes such as a stand-alone thioesterase and 2 methyltransferases. Inactivation of two cytochrome P(450) monooxygenase genes resulted in the production of acyclic spirangien derivatives, providing direct evidence for the involvement of these enzymes in spiroketal formation. The presence of large DNA repeats is consistent with multiple rounds of gene duplication during the evolution of the biosynthetic gene locus. 相似文献
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Hayato HosoiNobuyuki Kawai Hideki HagiwaraTakahiro Suzuki Atsuo NakazakiKen-ichi Takao Kazuo UmezawaSusumu Kobayashi 《Tetrahedron letters》2011,52(38):4961-4964
We describe the first total synthesis and structural determination of akaterpin, an inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC). The key features of the synthetic strategy include a regio- and stereoselective C-alkylation at the angular C1′ position and an exo-selective intermolecular Diels-Alder reaction. The relative stereochemistry was determined by a comparison of the NMR spectra of synthetic akaterpin with those of natural akaterpin. 相似文献
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Maloney DJ Deng JZ Starck SR Gao Z Hecht SM 《Journal of the American Chemical Society》2005,127(12):4140-4141
The first stereoselective total synthesis of the naturally occurring flavan myristinin A has been accomplished, as well as its biochemical evaluation. This synthesis verified the structural assignment and allowed for the determination of the absolute stereochemistry. Myristinin A exhibits biochemical activity both as a potent DNA-damaging agent and DNA polymerase beta inhibitor. Relaxation of supercoiled plasmid DNA was observed at picomolar concentrations, in addition to inhibition of polymerase beta at low micromolar concentrations. 相似文献
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[reaction: see text] An efficient two-pot, asymmetric synthesis of benzothiadiazine-substituted tetramic acids is reported. Starting from commercially available alpha-amino acids or esters, reductive amination followed by a novel one-pot amide bond formation/Dieckmann cyclization provided the desired products in high yield and optical purity. An analogous solid-phase approach to the same targets is also presented. These compounds were found to be potent inhibitors of hepatitis C virus RNA-dependent RNA polymerase. 相似文献
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Braisted AC Oslob JD Delano WL Hyde J McDowell RS Waal N Yu C Arkin MR Raimundo BC 《Journal of the American Chemical Society》2003,125(13):3714-3715
Using a site-directed fragment discovery method called tethering, we have identified a 60 nM small molecule antagonist of a cytokine/receptor interaction (IL-2/IL2Ralpha) with cell-based activity. Starting with a low micromolar hit, we employed a combination of tethering, structural biology, and computational analysis to design a focused set of 20 compounds. Eight of these compounds were at least 5-fold more active than the original hit. One of these compounds showed a 50-fold enhancement and represents the highest affinity inhibitor reported against this protein-protein target class. This method of coupling selected fragments with a low micromolar hit shows great potential for generating high-affinity lead compounds. 相似文献
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Paterson I Britton R Delgado O Wright AE 《Chemical communications (Cambridge, England)》2004,(6):632-633
The relative stereochemistry of the 22-membered marine macrolide dictyostatin, a Taxol-like antimitotic agent, was determined based on a combination of extensive high field NMR studies, including J-based configuration analysis, and molecular modelling. 相似文献
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Wilson KA Kalkum M Ottesen J Yuzenkova J Chait BT Landick R Muir T Severinov K Darst SA 《Journal of the American Chemical Society》2003,125(41):12475-12483
Microcin J25 (MccJ25) is a 21-amino acid peptide inhibitor active against the DNA-dependent RNA polymerase of Gram negative bacteria. Previously, the structure of MccJ25 was reported to be a head-to-tail circle, cyclo(-G(1)GAGHVPEYF(10)VGIGTPISFY(20)G-). On the basis of biochemical studies, mass spectrometry, and NMR, we show that this structure is incorrect, and that the peptide has an extraordinary structural fold. MccJ25 contains an internal lactam linkage between the alpha-amino group of Gly1 and the gamma-carboxyl of Glu8. The tail (Tyr9-Gly21) passes through the ring (Gly1-Glu8), with Phe19 and Tyr20 straddling each side of the ring, sterically trapping the tail in a noncovalent interaction we call a lassoed tail. 相似文献
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The bacterium Cupriavidus necator H16 produces a family of linear lipopeptides when grown under low iron conditions. The structural composition of these molecules, exemplified by the main metabolite cupriachelin, is reminiscent of siderophores that are excreted by marine bacteria. Comparable to marine siderophores, the ferric form of cupriachelin exhibits photoreactive properties. Exposure to UV light induces an oxidation of its peptidic backbone and a concomitant reduction of the coordinated Fe(III). Here, we report the genomics-inspired isolation and structural characterization of cupriachelin as well as its encoding gene cluster, which was identified by insertional mutagenesis. Based upon the functional characterization of adenylation domain specificity, a model for cupriachelin biosynthesis is proposed. 相似文献
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Jenny Barbier Dr. Rolf Jansen Dr. Herbert Irschik Dr. Stefan Benson Dr. Klaus Gerth Bettina Böhlendorf Prof. Dr. Gerhard Höfle Prof. Dr. Hans Reichenbach Jens Wegner Dr. Carsten Zeilinger Prof. Dr. Andreas Kirschning Prof. Dr. Rolf Müller 《Angewandte Chemie (International ed. in English)》2012,51(25):6035-6035