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91.
Jocelyne Enouf Françoise Lawrence Gisèle Farrugia Pierre Blanchard Malka Robert-Gero 《Archives of microbiology》1976,110(1):129-134
The bacteriostatic effect of methioninyl adenylate (MAMP)—a specific inhibitor of the enzyme methionyl-tRNA synthetase—was investigated on Salmonella typhimurium and Pseudomonas aeruginosa.0.1 mM of this molecule added to the culture, inhibits the growth of S. typhimurium. The inhibition is specifically reversible by 0.1 mM L-methionine. In the same conditions even 1–2 mM MAMP has a very slight effect on the growth rate of P. aeruginosa and only during the first two generations. The same observation was made with the two other members of the fluorescens group P. fluorescens and P. putida.The growth rate of P. testosteroni with 1 mM MAMP in the medium is similar to the growth rate of P. aeruginosa but the other member of the acidovorans group P. acidovorans is much more affected by the same concentration of the inhibitor. — P. multivorans is inhibited by MAMP like P. acidovorans but with a somewhat higher yield at the end of the culture.—MAMP has no effect on P. alcaligenes.The possible reasons for the weak bacteriostatic effect of MAMP on P. aeruginosa were investigated. It was established that the inhibitor enters the cells and is not used as a carbon and energy source. The intracellular methionine concentration in S. typhimurium and in P. aeruginosa is about the same and does not increase when bacteria are cultivated with MAMP. The MTS of the two microorganisms is inhibited by MAMP in vitro to about the same extent. Furthermore the tRNAmet from P. aeruginosa are fully acylated after 3 to 4 generations with this compound. Nevertheless MAMP elicits higher MTS activity in P. aeruginosa and in P. acidovorans after 1 h of incubation. The most striking difference between S. typhimurium and P. aeruginosa is that the intra and extracellular level of 5phosphodiesterase which degrades MAMP is 10–20 fold higher in the second than in the first species.Non Standard Abbreviations MAMP
Methioninyl adenylate
- MTS
methionyl-tRNA synthetase (EC 6.1.1.10)
- VTS
valyl-tRNA synthetase (EC 6.1.1.0)
- Tris
trihydroxymethylaminomethane
Dedicated to Prof. R. Y. Stanier on the occasion of his 60th birthday 相似文献
92.
93.
Sans résuméCentre de Recherches Hydrobiologiques du C.N.R.S. 相似文献
94.
Christopher J. Burns David G. Bourke Laura Andrau Xianyong Bu Susan A. Charman Andrew C. Donohue Emmanuelle Fantino Michelle Farrugia John T. Feutrill Max Joffe Marcel R. Kling Margarita Kurek Tracy L. Nero Thao Nguyen James T. Palmer Ian Phillips David M. Shackleford Harrison Sikanyika Michelle Styles Stephen Su Andrew F. Wilks 《Bioorganic & medicinal chemistry letters》2009,19(20):5887-5892
A series of phenylaminopyrimidines has been identified as inhibitors of Janus kinases (JAKs). Development of this initial series led to the potent JAK2/JAK1 inhibitor CYT387 (N-(cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]-benzamide). Details of synthesis and SAR studies of these compounds are reported. 相似文献
95.
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97.
LJ Melchers MJAM Clausen MF Mastik L Slagter-Menkema JE van der Wal GBA Wisman JLN Roodenburg E Schuuring 《Epigenetics》2015,10(9):850-860
Hypermethylation is an important mechanism for the dynamic regulation of gene expression, necessary for metastasizing tumour cells. Our aim is to identify methylation tumour markers that have a predictive value for the presence of regional lymph node metastases in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Significantly differentially expressed genes were retrieved from four reported microarray expression profiles comparing pN0 and pN+ head-neck tumours, and one expression array identifying functionally hypermethylated genes. Additional metastasis-associated genes were included from the literature. Thus genes were selected that influence the development of nodal metastases and might be regulated by methylation. Methylation-specific PCR (MSP) primers were designed and tested on 8 head-neck squamous cell carcinoma cell lines and technically validated on 10 formalin-fixed paraffin-embedded (FFPE) OOSCC cases. Predictive value was assessed in a clinical series of 70 FFPE OOSCC with pathologically determined nodal status. Five out of 28 methylation markers (OCLN, CDKN2A, MGMT,
MLH1 and DAPK1) were frequently differentially methylated in OOSCC. Of these, MGMT methylation was associated with pN0 status (P = 0.02) and with lower immunoexpression (P = 0.02). DAPK1 methylation was associated with pN+ status (P = 0.008) but did not associate with protein expression. In conclusion, out of 28 candidate genes, two (7%) showed a predictive value for the pN status. Both genes, DAPK1 and MGMT, have predictive value for nodal metastasis in a clinical group of OOSCC. Therefore DNA methylation markers are capable of contributing to diagnosis and treatment selection in OOSCC. To efficiently identify additional new methylation markers, genome-wide methods are needed. 相似文献
98.
99.
Fereydoun Ala Jean-Pierre Allain Imelda Bates Kamel Boukef Frank Boulton James Brandful Elizabeth M. Dax Magdy El Ekiaby Albert Farrugia Jed Gorlin Oliver Hassall Helen Lee Andr�� Loua Kathryn Maitland Dora Mbanya Zainab Mukhtar William Murphy Ohene Opare-Sem Shirley Owusu-Ofori Henk Reesink David Roberts Oscar Torres Grace Totoe Henrik Ullum Silvano Wendel 《PLoS medicine》2012,9(9)
100.
Ingrid J. G. Burvenich William Farrugia Fook T. Lee Bruno Catimel Zhanqi Liu Dahna Makris 《MABS-AUSTIN》2016,8(4):775-786
IgG has a long half-life through engagement of its Fc region with the neonatal Fc receptor (FcRn). The FcRn binding site on IgG1 has been shown to contain I253 and H310 in the CH2 domain and H435 in the CH3 domain. Altering the half-life of IgG has been pursued with the aim to prolong or reduce the half-life of therapeutic IgGs. More recent studies have shown that IgGs bind differently to mouse and human FcRn. In this study we characterize a set of hu3S193 IgG1 variants with mutations in the FcRn binding site. A double mutation in the binding site is necessary to abrogate binding to murine FcRn, whereas a single mutation in the FcRn binding site is sufficient to no longer detect binding to human FcRn and create hu3S193 IgG1 variants with a half-life similar to previously studied hu3S193 F(ab')2 (t1/2β, I253A, 12.23 h; H310A, 12.94; H435A, 12.57; F(ab')2, 12.6 h). Alanine substitutions in S254 in the CH2 domain and Y436 in the CH3 domain showed reduced binding in vitro to human FcRn and reduced elimination half-lives in huFcRn transgenic mice (t1/2β, S254A, 37.43 h; Y436A, 39.53 h; wild-type, 83.15 h). These variants had minimal effect on half-life in BALB/c nu/nu mice (t1/2β, S254A, 119.9 h; Y436A, 162.1 h; wild-type, 163.1 h). These results provide insight into the interaction of human Fc by human FcRn, and are important for antibody-based therapeutics with optimal pharmacokinetics for payload strategies used in the clinic. 相似文献