Eamon P Breen, Wayne Pilgrim, Kieran J Clarke, Cristy Yssel, Mark Farrell, Jian Zhou, Paul V Murphy, Richard K Porter
{"title":"Lack of activation of UCP1 in isolated brown adipose tissue mitochondria by glucose-O-ω-modified saturated fatty acids of various chain lengths.","authors":"Eamon P Breen, Wayne Pilgrim, Kieran J Clarke, Cristy Yssel, Mark Farrell, Jian Zhou, Paul V Murphy, Richard K Porter","doi":"10.1007/s12154-013-0093-6","DOIUrl":"https://doi.org/10.1007/s12154-013-0093-6","url":null,"abstract":"<p><p>We previously demonstrated that uncoupling protein 1 activity, as measured in isolated brown adipose tissue mitochondria (and as a native protein reconstituted into liposome membranes), was not activated by the non-flippable modified saturated fatty acid, glucose-O-ω-palmitate, whereas activity was stimulated by palmitate alone (40 nM free final concentration). In this study, we investigated whether fatty acid chain length had any bearing on the ability of glucose-O-ω-fatty acids to activate uncoupling protein 1. Glucose-O-ω-saturated fatty acids of various chain lengths were synthesized and tested for their potential to activate GDP-inhibited uncoupling protein 1-dependent oxygen consumption in brown adipose tissue mitochondria, and the results were compared with equivalent non-modified fatty acid controls. Here we demonstrate that laurate (12C), palmitate (16C) and stearate (18C) could activate GDP-inhibited uncoupling protein 1-dependent oxygen consumption in brown adipose tissue mitochondria, whereas there was no activation with glucose-O-ω-laurate (12C), glucose-O-ω-palmitate (16C), glucose-O-ω-stearate (18C), glucose-O-ω-arachidate (20C) or arachidate alone. We conclude that non-flippable fatty acids cannot activate uncoupling protein 1 irrespective of chain length. Our data further undermine the cofactor activation model of uncoupling protein 1 function but are compatible with the model that uncoupling protein 1 functions by flipping long-chain fatty acid anions. </p>","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"6 3","pages":"121-33"},"PeriodicalIF":0.0,"publicationDate":"2013-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-013-0093-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32035062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"JOCB Bulletin.","authors":"","doi":"10.1007/s12154-013-0092-7","DOIUrl":"https://doi.org/10.1007/s12154-013-0092-7","url":null,"abstract":"","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"6 2","pages":"77-84"},"PeriodicalIF":0.0,"publicationDate":"2013-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-013-0092-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32035096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei Xuan, Evan Murphy, Tom Beeckman, Dominique Audenaert, Ive De Smet
{"title":"Synthetic molecules: helping to unravel plant signal transduction.","authors":"Wei Xuan, Evan Murphy, Tom Beeckman, Dominique Audenaert, Ive De Smet","doi":"10.1007/s12154-013-0091-8","DOIUrl":"https://doi.org/10.1007/s12154-013-0091-8","url":null,"abstract":"<p><p>The application of small molecules has played a crucial role in identifying novel components involved in plant signalling. Compared to classic genetic approaches, small molecule screens offer notable advantages in dissecting plant biological processes, such as technical simplicity, low start-up costs, and most importantly, bypassing the problems of lethality and redundancy. To identify small molecules that target a biological process or protein of interest, robust and well-reasoned high-throughput screening approaches are essential. In this review, we present a series of principles and valuable approaches in small molecule screening in the plant model system Arabidopsis thaliana. We also provide an overview of small molecules that led to breakthroughs in uncovering phytohormone signalling pathways, endomembrane signalling cascades, novel growth regulators, and plant defence mechanisms. Meanwhile, the strategies to deciphering the mechanisms of these small molecules on Arabidopsis are highlighted. Moreover, the opportunities and challenges of small molecule applications in translational biology are discussed. </p>","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"6 2","pages":"43-50"},"PeriodicalIF":0.0,"publicationDate":"2013-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-013-0091-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32035095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synthetic circuit of inositol phosphorylceramide synthase in Leishmania : a chemical biology approach.","authors":"Vineetha Mandlik, Dixita Limbachiya, Sonali Shinde, Milsee Mol, Shailza Singh","doi":"10.1007/s12154-012-0089-7","DOIUrl":"https://doi.org/10.1007/s12154-012-0089-7","url":null,"abstract":"<p><p>Building circuits and studying their behavior in cells is a major goal of systems and synthetic biology. Synthetic biology enables the precise control of cellular states for systems studies, the discovery of novel parts, control strategies, and interactions for the design of robust synthetic systems. To the best of our knowledge, there are no literature reports for the synthetic circuit construction for protozoan parasites. This paper describes the construction of genetic circuit for the targeted enzyme inositol phosphorylceramide synthase belonging to the protozoan parasite Leishmania. To explore the dynamic nature of the circuit designed, simulation was done followed by circuit validation by qualitative and quantitative approaches. The genetic circuit designed for inositol phosphorylceramide synthase (Biomodels Database-MODEL1208030000) shows responsiveness, oscillatory and bistable behavior, together with intrinsic robustness. </p>","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"6 2","pages":"51-62"},"PeriodicalIF":0.0,"publicationDate":"2013-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-012-0089-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31996052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lipid-dependent and -independent regulation of nuclear envelope disassembly.","authors":"Marie-Charlotte Domart, Banafshé Larijani","doi":"10.1007/s12154-012-0088-8","DOIUrl":"https://doi.org/10.1007/s12154-012-0088-8","url":null,"abstract":"","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"6 1","pages":"3-5"},"PeriodicalIF":0.0,"publicationDate":"2012-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-012-0088-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31964068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"JOCB Bulletin.","authors":"","doi":"10.1007/s12154-012-0087-9","DOIUrl":"https://doi.org/10.1007/s12154-012-0087-9","url":null,"abstract":"","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"6 1","pages":"37-41"},"PeriodicalIF":0.0,"publicationDate":"2012-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-012-0087-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31964069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michele F Oliveira, Pedro P G Guimarães, Alinne D M Gomes, Diego Suárez, Rubén D Sinisterra
{"title":"Strategies to target tumors using nanodelivery systems based on biodegradable polymers, aspects of intellectual property, and market.","authors":"Michele F Oliveira, Pedro P G Guimarães, Alinne D M Gomes, Diego Suárez, Rubén D Sinisterra","doi":"10.1007/s12154-012-0086-x","DOIUrl":"https://doi.org/10.1007/s12154-012-0086-x","url":null,"abstract":"","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"6 1","pages":"7-23"},"PeriodicalIF":0.0,"publicationDate":"2012-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-012-0086-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31918368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Single-cell profiling of circulating tumour cells: a great leap forward.","authors":"Julien de Naurois","doi":"10.1007/s12154-012-0085-y","DOIUrl":"https://doi.org/10.1007/s12154-012-0085-y","url":null,"abstract":"","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"6 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2012-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-012-0085-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31867676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muthu K Kathiravan, Madhavi M Khilare, Aparna S Chothe, Madhuri A Nagras
{"title":"Design and development of topoisomerase inhibitors using molecular modelling studies.","authors":"Muthu K Kathiravan, Madhavi M Khilare, Aparna S Chothe, Madhuri A Nagras","doi":"10.1007/s12154-012-0079-9","DOIUrl":"https://doi.org/10.1007/s12154-012-0079-9","url":null,"abstract":"<p><p>Topoisomerase inhibitors are used as anticancer and antibacterial agents. A series of novel 2,4,6-tri-substituted pyridine derivatives reported as topoisomerase inhibitors were used for quantitative structure-activity relationship (QSAR) study. In order to understand the structural requirement of these topoisomerase inhibitors, a ligand-based pharmacophore and atom-based 3D-QSAR model have been developed. A five-point pharmacophore with one hydrophobic group (H4), four aromatic rings (R5, R6, R7 and R8) was obtained. The pharmacophore hypothesis yielded a 3D-QSAR model with good partial least-square (PLS) statistic results. The training set correlation is characterized by PLS factors (r (2) = 0.7892, SD = 0.2948, F = 49.9, P = 1.379). The test set correlation is characterized by PLS factors (q (2) = 0.7776, root mean squared error = 0.2764, Pearson R = 0.8926). The docking study revealed the binding orientations of these inhibitors at active site amino acid residues of topoisomerases enzyme. The results of pharmacophore hypothesis and 3D-QSAR provided the detail structural insights as well as highlighted the important binding features of novel 2,4,6-tri-substituted pyridine derivatives and can be developed as potent topoisomerase inhibitors. FigureKey structural requirement for topoisomerase activity. </p>","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"6 1","pages":"25-36"},"PeriodicalIF":0.0,"publicationDate":"2012-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-012-0079-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31769209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"JOCB Bulletin.","authors":"","doi":"10.1007/s12154-012-0081-2","DOIUrl":"https://doi.org/10.1007/s12154-012-0081-2","url":null,"abstract":"","PeriodicalId":15296,"journal":{"name":"Journal of Chemical Biology","volume":"5 4","pages":"167-75"},"PeriodicalIF":0.0,"publicationDate":"2012-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12154-012-0081-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31751861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}