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81.
We have determined the affinity of human deoxycytidine kinase with respect to new fluorescent N-methylanthraniloyl cytidine derivatives or non fluorescent enantiomeric cytidine analogues. New results regarding the enantioselectivity and the mechanism of the enzyme are presented. 相似文献
82.
D Egron C Périgaud G Gosselin A M Aubertin J L Imbach 《Nucleosides & nucleotides》1999,18(4-5):981-982
The synthesis and in vitro anti-HIV activity of tBuSATE phosphoramidate derivatives of AZT incorporating several methyl-esterified alpha-amino acids are reported. The biological evaluation strongly supports the hypothesis that such compounds exert their anti-HIV effects via intracellular delivery of the corresponding 5'-mononucleotide. 相似文献
83.
D Egron A A Arzumanov N B Dyatkina A Krayevsky J L Imbach A M Aubertin G Gosselin C Périgaud 《Nucleosides & nucleotides》1999,18(4-5):983-984
The synthesis, in vitro anti-HIV activity, and stability studies of AZT 5'-fluorophosphate (F-AZTMP) are reported. The present results demonstrate that such compound is a bioprecursor of its parent 5'-mononucleotide (AZTMP) but its biotransformation does not allow its selective intracellular delivery. Moreover, several attempts were carried out in order to improve the biological activity of this compound by the use of a SATE prodrug strategy. 相似文献
84.
An enzymatic method was developed for the preparation of unlabeled and [beta-32P]-labeled beta-L-2',3'-dd-5'ATP from the monophosphate with near quantitative yields. beta-L-2',3'-dd-5'ATP was a competitive and potent inhibitor of adenylyl cyclases (IC5 approximately 30 nM). Upon uv-irradiation beta-L-2',3'-dd-[beta-32P]-5'ATP directly crosslinked to a chimeric construct of this enzyme. Data suggest that this is a pre-transition state inhibitor and contrasts with the equipotent 2',5'-dd-3'ATP, a post-transition state, noncompetitive inhibitor. 相似文献
85.
S Gosselin B M Martin G J Murray T Viswanatha 《Journal of biochemical and biophysical methods》1992,24(1-2):71-79
Flavobacterium meningosepticum peptide:N-glycosidase-mediated deglycosylation of N-linked glycan strands of glycoproteins has been found to be strongly influenced by the ionic strength of the assay medium. By use of a modification of a previously published assay procedure for quantitative analysis of glycan release we have been able to improve reproducibility and thus to compare the extent of deglycosylation achieved under a variety of conditions of ionic strength. We have observed that enzyme activity is adversely affected by high ionic strength buffers such as those recommended for deglycosylation of various glycoproteins and recommend the use of low ionic strength buffers for routine use. 相似文献
86.
François-René Alexandre Eric Badaroux John P. Bilello Stéphanie Bot Tony Bouisset Guillaume Brandt Sylvie Cappelle Christopher Chapron Dominique Chaves Thierry Convard Clément Counor Daniel Da Costa David Dukhan Marion Gay Gilles Gosselin Jean-François Griffon Kusum Gupta Brenda Hernandez-Santiago Cyril B. Dousson 《Bioorganic & medicinal chemistry letters》2017,27(18):4323-4330
Herein we describe the discovery of IDX21437 35b, a novel RP d-aminoacid-based phosphoramidate prodrug of 2′-α-chloro-2′-β-C-methyluridine monophosphate. Its corresponding triphosphate 6 is a potent inhibitor of the HCV NS5B RNA-dependent RNA polymerase (RdRp). Despite showing very weak activity in the in vitro Huh-7 cell based HCV replicon assay, 35b demonstrated high levels of active triphosphate 6 in mouse liver and human hepatocytes. A biochemical study revealed that the metabolism of 35b was mainly attributed to carboxyesterase 1 (CES1), an enzyme which is underexpressed in HCV Huh-7-derived replicon cells. Furthermore, due to its metabolic activation, 35b was efficiently processed in liver cells compared to other cell types, including human cardiomyocytes. The selected RP diastereoisomeric configuration of 35b was assigned by X-ray structural determination. 35b is currently in Phase II clinical trials for the treatment of HCV infection. 相似文献
87.
The arrival of West Nile Virus in North America prompted public health authorities to develop intervention plans in order to prevent the propagation of this mosquito-transmitted pathogen. The last-resort measure proposed by the Government of Quebec (Canada) is the large-scale application of insecticides by aerial or ground Ultra Low Volume (ULV) treatment. This article presents an assessment of the exposure to malathion and its metabolite, malaoxon, for a population where an eventual application of malathion would occur. Each exposure pathway is detailed by describing the equation and every conservative assumption. This methodological framework was then used with the aim of assessing the toxicological risk based on a probabilistic approach (see companion article, this issue). In the current study, a daily absorbed dose of the mixture of malathion and malaoxon was estimated in terms of “malathion equivalent dose.” Each exposure pathway following a single event of ground or aerial ULV spraying of malathion was investigated for the population, classified into five age groups. Dermal exposure to dislodgeable residues on turf, foliage, and hard surfaces was estimated to be the most important source of exposure compared to any other pathways; it accounts for 63% to 98% of the estimated cumulative absorbed doses. The hand-to-mouth behavior of toddlers may also contribute considerably to their “malathion-equivalent” exposure (i.e., approximately 15% of the cumulative dose). Otherwise, the current study shows that ground ULV spraying is the type of treatment that may induce lower exposure, because the predicted concentration of malathion on turf and foliar surfaces is less than the one predicted for aerial ULV spraying. 相似文献
88.
Frédéric Gosselin 《Biodiversity and Conservation》2009,18(4):777-793
The case of the Northern spotted owl (Strix occidentalis caurina) has now become a classic case study in conservation biology, characterized by a harsh social battle but also by the quantity
and quality of the research performed. Based on this example, I study the way the research-management interface was organized.
The main lessons I have learned were: 1. laws that involve science in management are crucial but should be more precise; 2.
scientific ad-hoc groups are useful reviewers of management plans and interpreters of the best scientific data available,
even if more transparent scientific argumentation is needed on some points; 3. in such applied cases, even science that has
not been strongly integrated with management can produce results that are useful for management; 4. stronger links between
science and management appear necessary, but difficult to implement. This last point makes me wonder whether environmental
laws should not more frequently target the incorporation of science into the management process itself rather than “only”
basing management on the best scientific data available. On a more ecological level, perhaps the habitat issue has been underrated
during the last few years compared to other emerging threats such as the invasion of the spotted owl range by barred owls. 相似文献
89.
The stable population theory is classically applicable to populations in which there is a maximum age after which individuals die. Demetrius [1972. On an infinite population matrix. Math. Biosci. 13, 133-137] extended this theory to infinite Leslie matrices, in which the longevity of individuals is potentially infinite. However, Demetrius had to assume that the survival probability per time step tends to 0 with age. We generalise here the conditions of application of the stable population theory to infinite Leslie matrix models and apply these results to two examples, including or not senescence. 相似文献
90.
Marie Hamann Claire Pierra Jean-Pierre Sommadossi Chiara Musiu Luana Vargiu Michel Liuzzi Richard Storer Gilles Gosselin 《Bioorganic & medicinal chemistry》2009,17(6):2321-2326
Several thieno[3,4-d]pyrimidine derivatives, including four hitherto unknown 2′,3′-dideoxy- and 2′,3′-dideoxy-2′,3′-didehydro-C-nucleoside analogues of adenosine and inosine have been synthesized. When evaluated in cell culture experiments against human immunodeficiency virus, none of the tested compounds exhibited any significant antiviral effect, while two of them showed some cytotoxicity. 相似文献