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31.
Zakhari JS Kinoyama I Struss AK Pullanikat P Lowery CA Lardy M Janda KD 《Journal of the American Chemical Society》2011,133(11):3840-3842
The triphenyl amide/ester 12 was originally reported to be a potent mimic of the natural 3-oxo-dodecanoyl homoserine lactone quorum sensing molecule in Pseudomonas aeruginosa. However, explicit synthesis/chemical characterization was lacking, and a later report providing protein crystallographic data inferred 12 to be incorrect, with 9 now being the surmised structure. Because of these inconsistencies and our interest in quorum sensing molecules utilized by gram-negative bacteria, we found it necessary to synthesize 9 and 12 to test for agonistic activity in a P. aeruginosa reporter assay. Despite distinct regiochemical differences, both 9 and 12 were found to have comparable EC(50) values. To reconcile these unanticipated findings, modeling studies were conducted, and both compounds were revealed to have comparable properties for binding to the LasR receptor. 相似文献
32.
Garner AL Park J Zakhari JS Lowery CA Struss AK Sawada D Kaufmann GF Janda KD 《Journal of the American Chemical Society》2011,133(40):15934-15937
Multivalency is a common principle in the recognition of cellular receptors, and multivalent agonists and antagonists have played a major role in understanding mammalian cell receptor biology. The study of bacterial cell receptors using similar approaches, however, has lagged behind. Herein we describe our efforts toward the development of a dendrimer-based multivalent probe for studying AI-2 quorum-sensing receptors. From these studies, we have discovered a chemical probe specific for Lsr-type AI-2 quorum-sensing receptors with the potential for enabling the identification of new bacterial species that utilize AI-2 as a quorum-sensing signaling molecule. 相似文献
33.
Bacteria have developed a cell-to-cell communication system, termed quorum sensing (QS), which allows for the population-dependent coordination of their behavior via the exchange of chemical signals. Autoinducer-2 (AI-2), a class of QS signals derived from 4,5-dihydroxy-2,3-pentandione (DPD), has been revealed as a universal signaling molecule in a variety of bacterial species. In spite of considerable interest, the study of putative AI-2 based QS systems remains a challenging topic in part due to the rapid interconversion between the linear and cyclic forms of DPD. Herein, we report the design and development of efficient syntheses of carbocyclic analogues of DPD, which are locked in the cyclic form. The synthetic analogues were evaluated for the modulation of AI-2-based QS in Vibrio harveyi and Salmonella typhimurium. No agonists were uncovered in either V. harveyi or S. typhimurium assay, whereas weak to moderate antagonists were found against V. harveyi. On the basis of NMR analyses and DFT calculations, the heterocyclic oxygen atom within DPD appears necessary to promote hydration at the C3 position of cyclic DPD to afford the active tetrahydroxy species. These results also shed light on the interaction between the heterocyclic oxygen atom and receptor proteins as well as the importance of the linear form and dynamic equilibrium of DPD as crucial requirements for activation of AI-2 based QS circuits. 相似文献
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Lowery TJ Rubin SM Ruiz EJ Spence MM Winssinger N Schultz PG Pines A Wemmer DE 《Magnetic resonance imaging》2003,21(10):1235-1239
The chemical shift sensitivity and significant signal enhancement afforded by laser-polarized 129Xe have motivated the application of 129Xe NMR to biological imaging and spectroscopy. Recent research done by our group has used laser-polarized 129Xe in biomolecular assays that detect ligand-binding events and distinguish protein conformations. The successful application of unfunctionalized and functionalized 129Xe NMR to in vitro biomolecular assays suggests the potential future use of a functionalized xenon biosensor for in vivo imaging. 相似文献
36.
McKenzie KM Meijler MM Lowery CA Boldt GE Janda KD 《Chemical communications (Cambridge, England)》2005,(38):4863-4865
An autoinducer arising from reaction of cyclized S-DPD and carbonate is shown to induce light in V. harveyi and thus may play a previously unknown role in quorum sensing. 相似文献
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Bai JZ Bardon O Becker-Szendy RA Burnett TH Campbell JS Chen SJ Chen SM Chen YQ Cheng ZD Coller JA Cowan RF Cui HC Cui XZ Ding HL Du ZZ Dunwoodie W Fang C Fero MJ Gao ML Gao SQ Gao WX Gao YN Gu JH Gu SD Gu WX Guo YN Guo YY Han Y Hatanaka M He J Hitlin DG Hu GY Hu T Huang DQ Huang YZ Izen JM Jia QP Jiang CH Jiang ZJ Johnson AS Jones LA Kelsey MH Lai YF Lang PF Lankford A Li F Li J Li PQ Li QM Li RB Li W Li WD Li WG Li YS Lin SZ Liu HM Liu Q Liu RG Liu Y Lowery B Lu JG Ma DH Ma EC Ma JM 《Physical review letters》1992,69(21):3021-3024
39.
Mammalian skin is vulnerable to the photocarcinogenic and photoaging effects of solar UV radiation and defends itself using a variety of photoprotective responses including epidermal thickening, tanning and the induction of repair and antiradical systems. We treated Skh-1 albino hairless mice for 60 days with ultraviolet-A (UVA) or ultraviolet-B (UVB) radiation and measured the frequency of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts induced by a single acute sunburn dose of UVB at different stages of the chronic treatment. We found that both UVA and UVB exposure produced a photoprotective response in the dermis and epidermis and that the degree of photoproduct attenuation was dependent on dose, wavelength and the type of damage induced. Although epidermal thickening was important, our data suggest that UV protective compounds other than melanin may be involved in mitigating the damaging effects of sunlight in the skin. 相似文献
40.
Aimee A. Sanford Alexandra E. Rangel Trevor A. Feagin Robert G. Lowery Hector S. Argueta-Gonzalez Jennifer M. Heemstra 《Chemical science》2021,12(35):11692
Aptamers are widely employed as recognition elements in small molecule biosensors due to their ability to recognize small molecule targets with high affinity and selectivity. Structure-switching aptamers are particularly promising for biosensing applications because target-induced conformational change can be directly linked to a functional output. However, traditional evolution methods do not select for the significant conformational change needed to create structure-switching biosensors. Modified selection methods have been described to select for structure-switching architectures, but these remain limited by the need for immobilization. Herein we describe the first homogenous, structure-switching aptamer selection that directly reports on biosensor capacity for the target. We exploit the activity of restriction enzymes to isolate aptamer candidates that undergo target-induced displacement of a short complementary strand. As an initial demonstration of the utility of this approach, we performed selection against kanamycin A. Four enriched candidate sequences were successfully characterized as structure-switching biosensors for detection of kanamycin A. Optimization of biosensor conditions afforded facile detection of kanamycin A (90 μM to 10 mM) with high selectivity over three other aminoglycosides. This research demonstrates a general method to directly select for structure-switching biosensors and can be applied to a broad range of small-molecule targets.RE-SELEX is the first homogenous method for in vitro evolution of structure-switching DNA aptamers. 相似文献