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991.
Verena Thiel Brigitte Kunze Dr. Pankaj Verma Irene Wagner‐Döbler Prof. Dr. Stefan Schulz Prof. Dr. 《Chembiochem : a European journal of chemical biology》2009,10(11):1861-1868
N‐Acylhomoserine lactones (AHLs) are used by a wide variety of bacteria for cell–cell communication in “quorum‐sensing”. These compounds are derived from L ‐homoserine lactone and a fatty acid, which varies in chain‐length, degree of saturation, and the presence or absence of an oxygen atom at C‐3. In this study we describe for the first time the occurrence of acyl chains carrying a methyl branch, and present a GC‐MS‐based method that can be used to distinguish these compounds from unbranched isomers. The bacterium Aeromonas culicicola produces several methyl branched AHLs. In Jannaschia helgolandensis—a marine bacterium of the Roseobacter clade—a doubly unsaturated AHL, (2E,9Z)‐N‐(2,9‐hexadecadienoyl)‐L ‐homoserine lactone, occurs. The location and configuration of the double bonds was proven by spectrometric investigation and synthesis. Finally, a method was developed to establish the absolute configuration of 3‐hydroxyalkanoyl‐HSLs by mild cleavage and chiral gas chromatography. The AHLs synthesized during this study were tested in sensor systems specific for certain AHL types. The results show that these compounds display varying responses to the respective sensors; this underlines the importance of determining the whole bouquet of AHLs and its function to fully understand their importance for regulatory functions in bacteria. 相似文献
992.
Laura E. Pedró Rosa D. Rajasekhar Reddy Dr. Sherry F. Queener Prof. Lawrence W. Miller Prof. 《Chembiochem : a European journal of chemical biology》2009,10(9):1462-1464
Antifolate labels : Molecules that bind specifically and with high affinity to proteins can be developed into powerful tools for chemical biology. The interaction between substituted 5‐benzyl pyrimidines and dihydrofolate reductase can be exploited for chemically labeling fusion proteins in mammalian cells.
993.
Jens Ripcke Kim Zarse Michael Ristow Prof. Dr. Marc Birringer Dr. 《Chembiochem : a European journal of chemical biology》2009,10(10):1689-1696
Reversible mitochondrial shuttle : A novel concept in mitochondrial pharmacology allows the transport of bioactive compounds into the mitochondrial compartment and their subsequent release. A lipoic acid derivative containing a cleavable (“reversible”) triphenylphosphonium tag is endogenously cleaved by the mitochondrial aldehyde dehydrogenase (ALDH‐2) after mitochondrial accumulation.
994.
Kanchan Taori Yanxia Liu Dr. Valerie J. Paul Dr. Hendrik Luesch Prof. Dr. 《Chembiochem : a European journal of chemical biology》2009,10(10):1634-1639
Combinatorial biosynthesis meets combinatorial pharmacology, cyanobacterial style : A new antimitotic natural product with features of both dolastatins 10 and 15 was isolated from the same Floridian Symploca sp. sample that produced the histone deacetylase inhibitor largazole. Both agents in combination are more effective in inhibiting cancer cell proliferation than either agent alone.
995.
Monique van Scherpenzeel Ed E. Moret Dr. Lluis Ballell Dr. Rob M. J. Liskamp Prof. Dr. Ulf J. Nilsson Dr. Hakon Leffler Dr. Roland J. Pieters Dr. 《Chembiochem : a European journal of chemical biology》2009,10(10):1724-1733
Light up galectin: Photoprobes based on thiodigalactoside were prepared for galectin‐3, a lectin linked to cancer. The probes contained either benzophenone or acetophenone moieties as the photolabel for covalent attachment to the protein. One particular probe labeled galectin‐3 selectively, even in the presence of cell lysate.
996.
Chiaki Nakano Dr. Tsutomu Hoshino Prof. Dr. 《Chembiochem : a European journal of chemical biology》2009,10(12):2060-2071
The Rv3377c gene from the Mycobacterium tuberculosis H37 genome is specifically limited to those Mycobacterium species that cause tuberculosis. We have demonstrated that the gene product of Rv3377c is a diterpene cyclase that catalyzes the formation of tuberculosinol from geranylgeranyl diphosphate (GGPP). However, the characteristics of this enzyme had not previously been studied in detail with homogeneously purified enzyme. The purified enzyme catalyzed the synthesis of tuberculosinyl diphosphate from GGPP, but it did not bring about the synthesis of tuberculosinol. Optimal conditions for the highest activity were found to be as follows: pH 7.5, 30 °C, MgII (0.1 mM ), and Triton X‐100 (0.1 %). Under these conditions, the kinetic values of KM and kcat were determined to be 11.7±1.9 μM for GGPP and 12.7±0.7 min?1, respectively, whereas the specific activity was 186 nmol min?1 mg?1. The enzyme activity was inhibited at substrate concentrations higher than 50 μM . The catalytic activity was strongly inhibited by 15‐aza‐dihydrogeranylgeraniol and 5‐isopropyl‐N,N,N,2‐tetramethyl‐4‐(piperidine‐1‐carbonyloxy)benzenaminium chloride (Amo‐1618). The DXDTT293–297 motif, corresponding to the DXDDTA motif conserved among terpene cyclases, was mutated in order to investigate its function. The middle D295 was found to be the most crucial entity for the catalysis. D293 and two threonine residues function synergistically to enhance the acidity of D295, possibly through hydrogen‐bonding networks. The Rv3377c enzyme could also react with (14R/S)‐14,15‐oxidoGGPP to generate 3α‐ and 3β‐hydroxytuberculosinyl diphosphate. Conformational analyses were carried out with deuterium‐labeled GGPP and oxidoGGPP. We found that GGPP and (14R)‐oxidoGGPP adopted a chair/chair conformation, but (14S)‐oxidoGGPP adopted a boat/chair conformation. Interestingly, the conformations of oxidoGGPP for the A‐ring formation are the opposite of those of oxidosqualene when it is used as a substrate by squalene cyclases for the biosynthesis of hopene and tetrahymanol. (3R)‐Oxidosqualene is folded in a boat conformation, whereas (3S)‐2,3‐oxidosqualene folds into a chair conformation, for the formation of the A‐rings of the hopene and tetrahymanol skeletons, respectively. 相似文献
997.
998.
Arnold Grünweller Dr. Roland K. Hartmann Prof. Dr. 《Chembiochem : a European journal of chemical biology》2009,10(10):1599-1601
Silent partner : In a recent publication, Gunderson and co‐workers described an approach to recruit the abundant U1 snRNP, a splicing subparticle, to the last exon of a pre‐mRNA, in a sequence‐specific manner. This mediates interaction of the U1‐70K protein subunit with poly(A) polymerase, thus blocking polyadenylation and inducing pre‐mRNA degradation. This novel promising strategy expands the repertoire of gene‐silencing concepts.
999.
1000.
Norihito Muranaka Dr. Koichi Abe Yohei Yokobayashi Prof. 《Chembiochem : a European journal of chemical biology》2009,10(14):2375-2381
After the recent discovery of bacterial riboswitches, synthetic riboswitches have been engineered by using natural and artificial RNA aptamers. In contrast to natural riboswitches, the majority of synthetic riboswitches in bacteria reported to date are ON switches that activate gene expression in response to the aptamer ligand. In this study, we adopted a mechanism‐guided approach to design libraries predisposed to contain OFF riboswitches that respond to thiamine pyrophosphate (TPP). The first library design exploited a pseudo‐Shine‐Dalgarno (SD) sequence located near the 3′‐end of the TPP aptamer, which would be less accessible to the ribosome when the aptamer is bound to TPP. In the second library, an SD sequence was strategically placed in the aptamer's P1 stem, which is stabilized upon ligand binding. OFF riboswitches were obtained by dual genetic selection of these libraries. The results underscore the importance of effective library design to achieve desired riboswitch functions. 相似文献