Journal of enzyme inhibition最新文献

Progress Curves Analysis as an Alternative for Exploration of Activation-inhibition Phenomena in Cholinesterases 进展曲线分析作为探索胆碱酯酶激活-抑制现象的替代方法

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162388

Marko Golinik

{"title":"Progress Curves Analysis as an Alternative for Exploration of Activation-inhibition Phenomena in Cholinesterases","authors":"Marko Golinik","doi":"10.1080/14756360109162388","DOIUrl":"https://doi.org/10.1080/14756360109162388","url":null,"abstract":"The kinetic behaviour of insect acetylcholinesterases deviates from the Michaelis-Menten pattern. These deviations are known as activation or inhibition at various substrate concentrations and can be more or less observable depending on mutations around the active site of the enzyme. Most kinetic studies on these enzymes still rely on initial rate measurements. It is demonstrated here that according to this method one of the deviations can be overlooked. We attempt to point out that in such cases a detailed step-by-step progress curves analysis is successful. The study is focused on two different methods of analysing progress curves: (i) the first one is based on an integrated initial rate equation which can sufficiently fit truncated progress curves under corresponding conditions; and (ii) the other one precludes the algebraic formulae, but uses numerical integration for searching a non analytical solution of ordinary differential equations describing a kinetic model. All methods are tested on three different acetylcholinesterase mutants from Drosophila melanogaster. The results indicate that kinetic parameters for the E107K mutant with highly expressive activation and inhibition can be well evaluated applying any analysis method. It is quite different for E107W and E107Y mutants where latent activation is present, but discovered only using one or the other progress curves analysis methods.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"57 3","pages":"391 - 399"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72590648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Quantitative Structure-activity Relationship Study of Novel α1a-selective Adrenoceptor Antagonists 新型α1a选择性肾上腺素能受体拮抗剂的定量构效关系研究

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162381

P. Singh, R. Kumar

{"title":"Quantitative Structure-activity Relationship Study of Novel α1a-selective Adrenoceptor Antagonists","authors":"P. Singh, R. Kumar","doi":"10.1080/14756360109162381","DOIUrl":"https://doi.org/10.1080/14756360109162381","url":null,"abstract":"Two series of compounds were recently reported as novel α1a-selective adrenoceptor antagonists. In the first series, a dihydropyrimidone moiety is attached to a 4-phenyl piperidine containing side chain, while in the second, it is linked to a 4-substituted phenyl piperazine containing side chain. These compounds having potential for the treatment of benign prostatic hyperplasia, a urological disorder in the older age male population, were subjected to a quantitative structure-activity relationship study. The analysis has helped to ascertain the role of different substituents in explaining the observed binding potencies of these analogues. In the first category of compounds, three sites R1 R2 and X were varied and from the quantitative structure - activity relationship, it emerged that X- and R1-substituents having respectively, the high values of field and resonance effects may lead to more potent α1a-antagonists. The substituent of R2 being either CH3 or C2H5, does not add to improve the activity and thus the site, at present, becomes redundant. This site may, however, be explored for some additional substituents in future. In the second series of compounds, the phenyl ring, linked to a piperazine moiety at the end of a side chain, was substituted with various groups onto different positions. From derived significant correlations, it appeared the less polar and/or bulky substituents at the meta- and para-positions and a more hydrophobic substituent at the para-position are advantageous.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"39 1","pages":"331 - 338"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80523776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Probing the Active Site of Pea Seedlings Amine Oxidase with Optical Antipodes of Sedamine Alkaloids 用景莨菪碱光学对映体探测豌豆幼苗胺氧化酶活性位点

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162385

Ŝ. Adámková, I. Frébort, M. Šebela, P. Peč

引用次数: 5

Carbonic Anhydrase Inhibitors: Allylsulfonamide, Styrene Sulfonamide, N -allyl Sulfonamides and Some of Their Si, Ge, and B Derivatives 碳酸酐酶抑制剂:烯丙基磺酰胺、苯乙烯磺酰胺、N -烯丙基磺酰胺及其一些Si、Ge和B衍生物

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360127572

Céline Chazalette, M. Rivière-Baudet,, C. Supuran, A. Scozzafava

引用次数: 12

Inhibition of Chitin Synthetase from Saccharomyces cerevisiae by a New UDP-GlcNAc Analogue 一种新的UDP-GlcNAc类似物对酿酒酵母几丁质合成酶的抑制作用

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162360

J. Behr, Isabelle Gautier-Lefebvre, Claude Mvondo-Evina, G. Guillerm, N. Ryder

引用次数: 9

Structure-Activity Relationships of New NAPAP-Analogs 新型napap类似物的构效关系

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162372

T. Steinmetzer, Andrea Schweinttz, S. Künzel, Peter Wikstrsöm, J. Hauptmann, J. Stürzebecher

引用次数: 11

Isomerase Activity of the C-terminal Fructose-6-phosphate Binding Domain of Glucosamine-6-phosphate Synthase from Escherichia coli 大肠杆菌氨基葡萄糖-6-磷酸合酶c端果糖-6-磷酸结合域的异构酶活性

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162386

R. Todorova

引用次数: 1

Carbonic Anhydrase Inhibitors: Synthesis and Inhibition Against Isozymes I, II and IV of Topically Acting Antiglaucoma Sulfonamides Incorporating cis-5-Norbornene-endo-3-Carboxy-2-Carboxamido Moieties 碳酸酸酶抑制剂:含有顺式-5-降冰片烯-内3-羧基-2-羧基胺部分的局部作用抗青光眼磺胺类药物的合成和对同工酶I, II和IV的抑制

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162361

A. Casini, F. Mincione, M. Ilies, L. Menabuoni, A. Scozzafava, C. Supuran

{"title":"Carbonic Anhydrase Inhibitors: Synthesis and Inhibition Against Isozymes I, II and IV of Topically Acting Antiglaucoma Sulfonamides Incorporating cis-5-Norbornene-endo-3-Carboxy-2-Carboxamido Moieties","authors":"A. Casini, F. Mincione, M. Ilies, L. Menabuoni, A. Scozzafava, C. Supuran","doi":"10.1080/14756360109162361","DOIUrl":"https://doi.org/10.1080/14756360109162361","url":null,"abstract":"Sulfonamides incorporating cis-5-norbornene-endo-3-carboxy-2-carboxamido moieties in their molecules were prepared by reaction of cis-5-norbornene-endo-2,3-dicarboxylic anhydride with aromatic/heterocyclic sulfonamides possessing free amino, hydrazino, or imino groups. Some of these compounds showed very good CA II and CA IV inhibitory properties, with affinities for the enzymes in the low nanomolar range. Some of the most active CA II inhibitors reported here have been formulated as aqueous solutions for topical administration as antiglaucoma agents in normotensive rabbits. Some of the derivatives incorporating cis-5-norbornene-endo-3-carboxy-2-carboxamido and aromatic sulfonamide moieties (as sodium salts) showed effective and longer lasting intraocular pressure (IOP) lowering as compared to dorzolamide, a widely used topical antiglaucoma drug. Compounds incorporating cis-5-norbornene-endo-2,3-carboximido moieties, although stronger in vitro CA inhibitors as compared to the corresponding cis-5-norbomene-endo-3-carboxy-2-carbox-amido-derivatives, showed no topical IOP lowering properties, probably due to their very poor water solubility.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"2 1","pages":"113 - 123"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85342975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Modification of Human Erythrocyte Pyruvate Kinase by an Active Site-directed Reagent: Bromopyruvate 活性位点导向试剂溴丙酮酸修饰人红细胞丙酮酸激酶

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162395

N. Acan, N. Özer

引用次数: 11

Kinetics of Inactivation of Ulva pertusa Kjellm Alkaline Phosphatase by Ethylenediaminetetraacetic Acid Disodium 乙二胺四乙酸二钠对紫檀树碱性磷酸酶失活的动力学研究

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162379

Dong Yang, Jingyun Wang, Xiaojun Peng, L. An

引用次数: 0