The open enzyme inhibition journal最新文献

Coronavirus and Enzymes: What the Past Told us? 冠状病毒和酶:过去告诉我们什么?

The open enzyme inhibition journal Pub Date : 2020-04-03 DOI: 10.2174/0218749402005010001

Hortense Ferriz, R. Buchet

{"title":"Coronavirus and Enzymes: What the Past Told us?","authors":"Hortense Ferriz, R. Buchet","doi":"10.2174/0218749402005010001","DOIUrl":"https://doi.org/10.2174/0218749402005010001","url":null,"abstract":"Novelty always frightens, provoking overreactions. On the other hand, the strategy of viral infection, including that of coronavirus (COVID-19), originates from ancient times and can be summarized, as 1) entry into host cells, 2) interfering with host genetic program to duplicate virus entity; 3) infection into surrounding cells. These are the strengths of the viruses but also their weaknesses since it identifies possible targets to prevent infection. At each step of viral infection, viral enzymatic reactions are observed, which may be similar to those occurring in another closely related family of viruses. COVID-19 is related with 88% to two bat-derived severe acute respiratory syndromes (SARS)-like coronaviruses (bat-SLCoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China), SARS-CoV (about 79%) and MERS-CoV (about 50%) [1]. The penetration of the COVID-19, similar to that of SARS-CoV, into the infected cells is triggered by the interaction of a protein on the surface of the virus with a receptor angiotensin-converting enzyme 2 (ACE2) on the infected cells [2]. Preventing interaction between the viral protein on its surface and the cell receptor, using a soluble version of the viral receptor, angiotensinconverting enzyme 2 fused to an immunoglobulin Fc domain, is a proposed plan to prevent coronavirus infection [3]. This modified ACE2 will selectively interact with the viral protein and not with the cell, protecting physiological function of ACE2 [3]. Several viral enzymes are possible targets to design drugs for stopping viral infections. Once the virus penetrates into the host cell, it interferes with the genetic program. Possible target is the viral RNA-dependent RNA polymerases to avoid viral duplication. Remdesivir, a nucleotide analog, can inhibit the viral RNA-dependent RNA polymerase and had broad spectrum of antiviral activities against several RNA viruses including SARS-CoV and MERSCoV [4], stimulating hope that Remdesivir treatment could be also effective to treat","PeriodicalId":89033,"journal":{"name":"The open enzyme inhibition journal","volume":"5 1","pages":"1-1"},"PeriodicalIF":0.0,"publicationDate":"2020-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41805768","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: 1

Assessing PCR Inhibition from Humic Substances 评估腐殖质对PCR的抑制作用

The open enzyme inhibition journal Pub Date : 2014-07-11 DOI: 10.2174/1874940201003010038

C. Matheson, Carli Gurney, N. Esau, Ryan Lehto

{"title":"Assessing PCR Inhibition from Humic Substances","authors":"C. Matheson, Carli Gurney, N. Esau, Ryan Lehto","doi":"10.2174/1874940201003010038","DOIUrl":"https://doi.org/10.2174/1874940201003010038","url":null,"abstract":"Inhibition remains the greatest methodological challenge in molecular analysis of buried biological remains. Inhibitory compounds associated with soil environments comprise primarily of humic acids and fulvic acids, collectively referred to as humic substances. We examined the sensitivity of 13 DNA polymerases to both humic acids (11ng-110� g) and fulvic acids (9.4ng-94� g) and the concentration at which successful amplification can be achieved. This research identified that all 13 DNA polymerases tested exhibited inhibition with varying concentrations of humic acids and that 5 out of the 13 DNA polymerase tested exhibited inhibition with varying concentrations of fulvic acid. The most tolerant DNA polymerase to inhibition due to the presence of humic and fulvic acids is pfu DNA polymerase followed by KlenTaq ® LA DNA polymerase and RealTaq DNA polymerase that were both only inhibited by 11� g and 110� g of humic acids. In addition, we present the use of size exclusion chromatography to remove small molecular weight humic substance, dramatically increasing the success of molecular analysis on material associated with burial. This research has implications to the fields of environmental microbiology, soil science, forensic science and archaeological science.","PeriodicalId":89033,"journal":{"name":"The open enzyme inhibition journal","volume":"3 1","pages":"38-45"},"PeriodicalIF":0.0,"publicationDate":"2014-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68096052","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: 121

Study of the Selectivity of Insulin-Like Growth Factor-1 Receptor (IGF1R) Inhibitors 胰岛素样生长因子-1受体抑制剂的选择性研究

The open enzyme inhibition journal Pub Date : 2014-07-11 DOI: 10.2174/1874940201003010027

P. Chène, J. Hau, Anke Blechschmidt, P. Fontana, J. Bohn, C. Zimmermann, A. Pover, D. Erdmann

{"title":"Study of the Selectivity of Insulin-Like Growth Factor-1 Receptor (IGF1R) Inhibitors","authors":"P. Chène, J. Hau, Anke Blechschmidt, P. Fontana, J. Bohn, C. Zimmermann, A. Pover, D. Erdmann","doi":"10.2174/1874940201003010027","DOIUrl":"https://doi.org/10.2174/1874940201003010027","url":null,"abstract":"The insulin-like growth factor-1 receptor (IGF1R) is a drug target for oncology, and many studies are ongoing to identify compounds that inhibit its tyrosine kinase activity. IGF1R is highly homologous to the insulin receptor (IR) and IGF1R inhibition might be beneficial for patients, while IR inhibition may lead to limiting toxicity. Therefore selectivity for IGF1R over IR is the aim for drug design in this context. A few compounds that selectively inhibit IGF1R over IR in cells have been identified, but none of them show the same levels of selectivity in enzymatic assays. To deter- mine whether this discrepancy is linked to the conditions used in the enzymatic assays, we have studied the interaction be- tween known IGF1R inhibitors (NVP-AEW541, OSI906, AG538, NVP-TAE226) and phosphorylated/unphosphorylated IGF1R/IR proteins with both biophysical (isothermal calorimetry and surface plasmon resonance) and enzymatic methods. In this report, we describe the results of this study and comment on the different degrees of selectivity IGF1R versus IR measured in biochemical and cellular assays. Finally, our study provides new information on the biochemical and mechanism of action of these small molecular weight IGF1R inhibitors.","PeriodicalId":89033,"journal":{"name":"The open enzyme inhibition journal","volume":"3 1","pages":"27-37"},"PeriodicalIF":0.0,"publicationDate":"2014-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68096037","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: 2

Characterization, Modes of Synthesis, and Pleiotropic Effects of Hypocholesterolemic Compounds – A Review 低胆固醇化合物的表征、合成方式和多效性——综述

The open enzyme inhibition journal Pub Date : 2011-11-16 DOI: 10.2174/1874940201104010023

A. Seenivasan, T. Panda, T. Théodore

{"title":"Characterization, Modes of Synthesis, and Pleiotropic Effects of Hypocholesterolemic Compounds – A Review","authors":"A. Seenivasan, T. Panda, T. Théodore","doi":"10.2174/1874940201104010023","DOIUrl":"https://doi.org/10.2174/1874940201104010023","url":null,"abstract":"Studies on the various cholesterol-lowering agents is one of the important areas in clinical research. Identifica- tion and characterization of potential molecules from various sources have been carried out in the past and their relation- ship with the enzymes which are involved in the cholesterol cascade is gaining interest. In this review, we have high- lighted various inhibitors involved in the cholesterol cascade as well as cholesterol-lowering agents, viz., tocotrienol, flavonoids, phytosterols, phytostanols, statins, DADS, and synthetic compounds. The mechanism of action and characteri- zation of these hypocholesterolemic compounds are discussed in this communication. Major natural sources as well as synthetic and biological routes of synthesis of these compounds are reviewed in a concise manner. Especially, various HMG-CoA analogues including statins have been reviewed specifically. In this respect, researchers have identified 2,3- oxidosqualene cyclase-lanosterol synthase (lanosterol syn- thase, oxidosqualene-lanosterol cyclase, lanosterol synthase, 2,3-oxidosqualene-lanosterol cyclase, human lanosterol syn- thase (EC 5.4.99.7)) having a molecular weight of 83 kDa, catalyzing the highly selective cyclization reaction from the substrate 2,3-oxidosqualene (squalene 2,3-epoxide, squalene 2,3-oxide, (S)-squalene-2,3-epoxide, 2,3-epoxisqualene, oxidosqualene) into lanosterol, as an appropriate step for the inhibition of cholesterol biosynthesis (3). Oxidosqualene cyclase inhibitors (OSCI) arrest the downstream of 2,3- oxidosqualene which helps to stimulate epoxysterols to","PeriodicalId":89033,"journal":{"name":"The open enzyme inhibition journal","volume":"4 1","pages":"23-32"},"PeriodicalIF":0.0,"publicationDate":"2011-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68095761","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

Identification of Potent and Selective Human Ecto-Nucleotide Pyrophosphatase/Phosphodiesterase-3 (hNPP3) Inhibitors 强效和选择性人外核苷酸焦磷酸酶/磷酸二酯酶-3 (hNPP3)抑制剂的鉴定

The open enzyme inhibition journal Pub Date : 2011-10-27 DOI: 10.2174/1874940201104010017

Rabia Raza, T. Akhtar, S. Hameed, J. Lecka, J. Iqbal, J. Sévigny

引用次数: 7

Insights into the Chloramphenicol Inhibition Effect on Peptidyl Transferase Activity, Using Two New Analogs of the Drug 利用两种新的药物类似物研究氯霉素对肽基转移酶活性的抑制作用

The open enzyme inhibition journal Pub Date : 2011-04-28 DOI: 10.2174/1874940201104010001

O. N. Kostopoulou, T. Kourelis, P. Mamos, George E. Magoulas, D. Kalpaxis

{"title":"Insights into the Chloramphenicol Inhibition Effect on Peptidyl Transferase Activity, Using Two New Analogs of the Drug","authors":"O. N. Kostopoulou, T. Kourelis, P. Mamos, George E. Magoulas, D. Kalpaxis","doi":"10.2174/1874940201104010001","DOIUrl":"https://doi.org/10.2174/1874940201104010001","url":null,"abstract":"Chloramphenicol (CAM) inhibits peptide bond formation by binding to the 50S subunit of prokaryotic ribosomes and interfering competitively with the binding of the aminoacyl-tRNA 3'- terminus to ribosomal A-site. Further studies have demonstrated that CAM (I) reacts rapidly with a model initiator ribosomal complex (poly(U)-programmed ribosomes from Escherichia coli, bearing AcPhe-tRNA at the P-site), complex C, to form an encounter complex CI which is then isomerized slowly to a tighter complex, C ￻ I. Herein, we show by time-resolved footprinting analysis that CAM produces a footprint in CI complex, comprising nucleotides A2451, G2505, and U2506, all exhibiting reduced reactivity against base-specific modifying agents. When C ￻ I complex is footprinted, the reactivities of G2505 and U2506 are almost restored, while protection is observed at A2062 and altered reactivity at A2058 and A2059. Our results suggest that CAM initially binds to a hydrophobic crevice composed of nucleotides located adjacently to the A-site (CI complex). Soon after, CAM shifts slowly to a final position, in which the interaction between the p-nitrobenzyl group of CAM and the base of A2451 is conserved, while the dichloroacetyl group reorientates toward A2062. Analogous behavior is observed, if CAM is modified by replacement of dichloroacetyl group with � -alanyl. However, insertion at this position of a bulkier group, such as phenylalanyl-phenylalanyl group, sterically prevents CAM accommodation to its initial binding site and favors its direct fitting into the final binding pocket. Our data correlate well with recent crystallographic results regarding CAM binding on Thermus thermophilus and E. coli ribosomes.","PeriodicalId":89033,"journal":{"name":"The open enzyme inhibition journal","volume":"4 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2011-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68096149","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: 14

The Cathepsin B-Selective Inhibitors CA-074 and CA-074Me Inactivate Cathepsin L Under Reducing Conditions 组织蛋白酶b选择性抑制剂CA-074和CA-074Me在还原条件下使组织蛋白酶L失活

The open enzyme inhibition journal Pub Date : 2011-04-28 DOI: 10.2174/1874940201104010011

D. Steverding

引用次数: 30

Targeting Cancer by Inducing Senescence 通过诱导衰老靶向癌症

The open enzyme inhibition journal Pub Date : 2010-12-01 DOI: 10.2174/1874940201003010046

Juan J. Marin, Mar Vergel, A. Carnero

引用次数: 12

Inhibition Kinetics of Agaricus bisporus (J.E. Lange) Imbach Polyphenol Oxidase 双孢蘑菇对Imbach多酚氧化酶的抑制动力学

The open enzyme inhibition journal Pub Date : 2010-03-12 DOI: 10.2174/1874940201003010001

H. Gouzi, T. Coradin, E. Delicado, M. Unal, A. Benmansour

引用次数: 15

Inhibitors of Pyruvate Carboxylase. 丙酮酸羧化酶抑制剂。

The open enzyme inhibition journal Pub Date : 2010-01-01 DOI: 10.2174/1874940201003010008

Tonya N Zeczycki, Martin St Maurice, Paul V Attwood

引用次数: 0