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91.
应用N-酰基高丝氨酸内酯(N-acyl-L-homoserine lactones,AHL)介导的群体感应(quorum sensing,QS)系统调控生物膜形成和次级代谢物合成具有巨大的商业价值,但自然界中许多微生物能够产生群体淬灭(Quorum Quenching,QQ)酶,QQ酶能够降解天然AHL信号分子,使外源天然 AHL 信号分子的半衰期缩短,限制了天然AHL 信号分子的应用范围。化学合成的AHL类似物作为QS促进剂,通过与天然信号分子类似的结合方式形成转录二聚体,激活下游基因表达,但与天然AHL信号分子相比,化学合成的QS促进剂具有活性高、半衰期长等优点。本文综述了化学合成AHL类似物的设计思路、种类、作用机制及其在提高次级代谢物产量和生物浸矿方面的应用,并讨论了QS促进剂今后主要的研究方向,以期为QS促进剂的合成设计和实际应用提供参考。 相似文献
92.
Julia Khairulina Dmitri Graifer Konstantin Bulygin Aliya Ven'yaminova Ludmila Frolova Galina Karpova 《Biochimie》2010
The eukaryotic ribosomal protein S15 is a key component of the decoding site in contrast to its prokaryotic counterpart, S19p, which is located away from the mRNA binding track on the ribosome. Here, we determined the oligopeptide of S15 neighboring the A site mRNA codon on the human 80S ribosome with the use of mRNA analogues bearing perfluorophenyl azide-modified nucleotides in the sense or stop codon targeted to the 80S ribosomal A site. The protein was cross-linked to mRNA analogues in specific ribosomal complexes that were obtained in the presence of eRF1 in the experiments with mRNAs bearing stop codon. Digestion of modified S15 with various specific proteolytic agents followed by identification of the resulting modified oligopeptides showed that cross-link was in C-terminal fragment in positions 131–145, most probably, in decapeptide 131-PGIGATHSSR-140. The position of cross-linking site on the S15 protein did not depend on the nature of the A site-bound codon (sense or stop codon) and on the presence of polypeptide chain release factor eRF1 in the ribosomal complexes with mRNA analogues bearing a stop codon. The results indicate an involvement of the mentioned decapeptide in the formation of the ribosomal decoding site during elongation and termination of translation. Alignment of amino acid sequences of eukaryotic S15 and its prokaryotic counterpart, S19p from eubacteria and archaea, revealed that decapeptide PGIGATHSSR in positions 131–140 is strongly conserved in eukaryotes and has minor variations in archaea but has no homology with any sequence in C-terminal part of eubacterial S19p, which suggests involvement of the decapeptide in the translation process in a eukaryote-specific manner. 相似文献
93.
The absolute configurations of three synthesized anthracycline analogues have been determined using vibrational circular dichroism (VCD) spectroscopy and the density functional theory (DFT) calculations. The experimental VCD spectra of the three compounds have been measured for the first time in the film state, prepared from their CDCl3 solutions. Conformational searches for the monomers and some dimers of the three compounds have been performed at the DFT level using the B3LYP functional and the 6‐311G** and 6‐311++G** basis sets. The corresponding vibrational absorption and VCD spectra have been calculated. The good agreement between the experimental and the calculated spectra allows one to assign the absolute configurations of the three compounds with high confidence. In addition, the dominant conformers of the three compounds have also been identified. Chirality, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
94.
95.
S. I. Selivanov A. Yu. Solov’ev S. N. Morozkina A. G. Shavva 《Russian Journal of Bioorganic Chemistry》2007,33(3):302-309
All the signals in the 1H and 13C NMR spectra of some analogues of 7α-methyl-8α-and 6-oxa-8α-steroid estrogens were completely assigned. Considering the values of nuclear Overhauser effect and vicinal coupling constants, these steroids were shown to exhibit a fast, on the NMR time scale, conformational equilibrium arising due to the inversion of ring B. The conformer populations were obtained from a comparison of the experimental and theoretical values of the dihedral angles and the interproton distances. This conformational equilibrium was shown to depend on the nature of atom in position 6: for the 7α-methyl-6-oxa-8α analogues of the steroid estrogens, the population of the conformer with the pseudoaxial orientation of the 7α-methyl group was observed to be decreased compared with the 7α-methyl-8α analogue. 相似文献
96.
N‐terminal guanidinylation of the cyclic 1,4‐ureido‐deltorphin analogues: the synthesis,receptor binding studies,and resistance to proteolytic digestion
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Krzysztof Bańkowski Olga M. Michalak Anna Leśniak Katarzyna E. Filip Piotr Cmoch Zbigniew Szewczuk Piotr Stefanowicz Jan Izdebski 《Journal of peptide science》2015,21(6):467-475
The synthesis of a series of N‐guanidinylated cyclic ureidopeptides, analogues of 1,4‐ureido‐deltorphin/dermorphine tetrapeptide is described. The δ‐ and μ‐opioid receptor affinity of new guanidinylated analogues and their non‐guanidinylated precursors was determined by the displacement radioligand binding experiments. Our results indicate that the guanidinylation of cyclic 1,4‐ureidodeltorphin peptide analogues does not exhibit a uniform influence on the opioid receptor binding properties, similarly as reported earlier for some linear peptides. All analogues were also tested for their in vitro resistance to proteolysis during incubation with large excess of chymotrypsin, pepsin, and papain by means of mass spectroscopy. Guanidinylated ureidopeptides 1G–4G showed mixed μ agonist/δ agonist properties and high enzymatic stability indicating their potential as therapeutic agents for treatment of pain. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
97.
Gao J Li X Gu G Sun B Cui M Ji M Lou HX 《Bioorganic & medicinal chemistry letters》2011,21(2):622-627
To investigate the relationship of cytotoxicity and saponins with varied aglycones, based on the structure of indioside E 1, a natural derived anti-tumor active ingredient from Chinese medicinal plant Solanum indicum L., five novel saponins 2-6 bearing the same trisaccharide moiety together with 1 were efficiently synthesized via a transglycosylation strategy. MTT assay revealed the killing effects to tumor cells of the synthesized saponins are varied with the change of aglycones. Furthermore, time-lapse microscopy, LDH release, PI staining, and immunocytochemical investigations demonstrated that the cell death caused by neosaponin 2 was through oncotic necrosis involving plasma membrane perturbation and destruction of cytoskeleton. 相似文献
98.
Chen W Xu L Cai L Zheng B Wang K He J Liu K 《Bioorganic & medicinal chemistry letters》2011,21(19):5762-5764
The Hotoda’s sequence substituted with TBDPS via 5′-end nucleobase existed as parallel quadruplex structure and exhibited inhibitory activities in an HIV-1 envelop proteins mediated cell-cell fusion assay. This result demonstrated that the 5′-aromatic groups of the Hotoda’s sequence are allowed to have a large spatial freedom and remain to be optimized for its role in the binding to HIV-1 envelop proteins. 相似文献
99.
Huang LH Wang YG Xu G Zhang XH Zheng YF He HL Fu WZ Liu HM 《Bioorganic & medicinal chemistry letters》2011,21(20):6203-6205
A series of novel N-glycoside analogues with 4-azasteroid moiety bearing sugar-like D ring were conveniently synthesized by constructing the core dihydropyran ring embedded in 4-azasteroidal skeleton which was prepared from 4-aza-5α-androst-3,17-dione 1 in four steps. The structure of 6b were unambiguously proved by the appropriate X-ray structural analysis. Anticancer activity was found for all of the analogues with purinyl moiety against breast cancer (MCF-7), human neuroblastoma (SK-N-SH), cervical cancer cell (HeLa) and prostatic cancer (PC-3), while the analogue 7 containing 1,2,4-triazole heterocycle as the nucleobase was inactive against all of the tested cancer cell lines. The biology results showed the purinyl moiety attached to the pyran ring of 6a-d, substituent at 6'-position of purine base and introduction of a halogen atom at 2'-position of 6'-chloropurine had obviously effect on the evaluated anticancer activity. 相似文献
100.
Harper JL Hayman CM Larsen DS Painter GF Singh-Gill G 《Bioorganic & medicinal chemistry》2011,19(2):917-925
Two approaches for the synthesis of a phosphatidylinositol dimannoside (PIM2) analogue 4 that mimics the suppressive activity of natural PIMs and also synthetic PIM2 have been developed. This analogue, where the inositol core was replaced by glycerol, was tested for its ability to suppress cellular inflammation in a mouse model of allergic asthma and shown to be effective in suppressing airway eosinophilia. Suppression of all inflammatory cells monitored was observed, indicating a general blockade of cellular activity. These data indicate that the inositol core is not essential for this suppressive activity. 相似文献