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Conception, synthèse et évaluation pharmacologique d'inhibiteurs de DD-ligases
Authors: --- ---
Year: 2016 Publisher: Bruxelles: UCL. Faculté de pharmacie et des sciences biomédicales,

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La résistance bactérienne aux antibiotiques constitue une menace croissante pour la santé publique. La découverte de nouvelles molécules à action antibactérienne s’impose désormais comme une nécessité. Parmi les cibles potentielles dans le cadre du développement de nouveaux antibiotiques, les DD-ligases sont tout particulièrement intéressantes. Ces enzymes bactériennes agissent au niveau de la synthèse cytoplasmique du peptidoglycane. Elles sont de ce fait essentielles à la formation de la paroi cellulaire et par extension à la croissance bactérienne. Le développement d’inhibiteurs de DD-ligases est donc d’un intérêt certain dans l’optique de recherche de nouveaux antibiotiques. Un inhibiteur original de ces DD-ligases, au motif thiosemicarbazide central, a été identifié lors de précédents recherches au sein du département de chimie médicinale de la Louvain Drug Research institute. Le travail présenté ici s’est attelé à approfondir l’étude de ce motif. Pour ce faire, une chimiothèque d’une vingtaine d’analogues au motif thiosemicarbazide a tout d’abord été synthétisée, analysée et purifiée. La puissance ainsi que le mode d’inhibition de ces composés ont ensuite été évalués sur une DD-ligase, la D-Ala-D-Ala ligase. L’évaluation pharmacologique de ces molécules a été réalisée grâce à un test enzymatique lui-même développé dans le cadre de cette étude. Enfin, à la lumière des résultats obtenus, une nouvelle série d’inhibiteurs originaux a été synthétisée et testée sur la Ddl. As antimicrobial resistance is becoming an uprising public health issue, the development of new antibiotics appears to be increasingly urgent. Among potential targets for new antimicrobial agents, the DD-ligases constitute a promising one. These enzymes act in an early step of peptidoglycan synthesis and are therefore essential for bacterial growth. The past few years have allowed the medicinal chemistry department of the Louvain Drug Research lnstitute to develop its expertise in the research of new pharmacological tools able to successfully inhibit the DD-ligases. More recently, a promising molecule bearing a thiosemicarbazide scaffold has emerged from the screening of an in-house library. This inhibitor exhibits a good potency against DD-ligases as well as a promising antimicrobial activity. The work herein focused on studying the thiosemicarbazide moiety as an interesting scaffold in targeting DD-ligases. To do so, a set of 20 thiosemicarbazides analogues were first successfully synthetized and analyzed for both their structures and purities. These molecules were then tested for their activities on one DD­ ligase, the D-Ala-D-Ala ligase. The pharmacological evaluation of the thiosemicarbazides analogues was made possible by an enzymatic assay able to measure the ligase activity, also developed within this project. Finally, the results previously obtained allowed us to synthetize and evaluate a new set of originals inhibitors of DD-ligases.


Book
New-Generation Bioinorganic Complexes
Authors: --- --- --- --- --- et al.
ISBN: 311034890X 3110386445 9783110348910 3110348918 9783110348903 9783110386448 9783110348804 3110348802 Year: 2016 Publisher: Berlin Boston

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Bio-Inorganic compounds are successfully applied as therapeutic agents since decades. Thus, scientist designed new metal complexes bearing biomolecules as ligands, investigating their potential as bioactive and therapeutic agents. This book presents a comprehensive overview on materials design, substance classes and their characterization. This book is compiled for scientists interested in medical application of bioinspired materials.


Book
Amino Acids of the Glutamate Family: Functions beyond Primary Metabolism
Authors: --- --- ---
Year: 2016 Publisher: Frontiers Media SA

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The life of proteins starts and ends as amino acids. In addition to the primary function as protein building blocks, amino acids serve multiple other purposes to make a plant's life worth living. This is true especially for the amino acids of the glutamate family, namely glutamate (Glu), glutamine (Gln), proline (Pro) and arginine (Arg), as well as the product of Glu decarboxylation, ?-aminobutyric acid (GABA). Synthesis, accumulation, interconversion and degradation of these five compounds contribute in many ways to the regulation of plant development and to responses to environmental challenges. Glu and Gln hold key positions as entry points and master regulators of nitrogen metabolism in plants, and have a pivotal role in the regulatory interplay between carbon and nitrogen metabolism. Pro and GABA are among the best-studied compatible osmolytes that accumulate in response to water deficit, yet the full range of protective functions is still to be revealed. Arg, with its exceptionally high nitrogen-to-carbon ratio, has long been recognized as a major storage form of organic nitrogen. Most of the enzymes involved in metabolism of the amino acids of the glutamate family in plants have been identified or can be predicted according to similarity with animal or microbial homologues. However, for some of these enzymes the detailed biochemical properties still remain to be determined in order to understand activities in vivo. Additionally, uncertainties regarding the subcellular localization of proteins and especially the lack of knowledge about intracellular transport proteins leave significant gaps in our understanding of the metabolic network connecting Glu, Gln, Pro, GABA and Arg. While anabolic reactions are distributed between the cytosol and chloroplasts, catabolism of the amino acids of the glutamate family takes place in mitochondria and has been implicated in fueling energy-demanding physiological processes such as root elongation, recovery from stress, bolting and pollen tube elongation. Exceeding the metabolic functions, the amino acids of the glutamate family were recently identified as important signaling molecules in plants. Extracellular Glu, GABA and a range of other metabolites trigger responses in plant cells that resemble the actions of Glu and GABA as neurotransmitters in animals. Plant homologues of the Glu-gated ion channels from mammals and protein kinase signaling cascades have been implicated in these responses. Pollen tube growth and guidance depend on GABA signaling and the root architecture is specifically regulated by Glu. GABA and Pro signaling or metabolism were shown to contribute to the orchestration of defense and programmed cell death in response to pathogen attacks. Pro signaling was additionally proposed to regulate developmental processes and especially sexual reproduction. Arg is tightly linked to nitric oxide (NO) production and signaling in plants, although Arg-dependent NO-synthases could still not be identified. Potentially Arg-derived polyamines constitute the missing link between Arg and NO signaling in response to stress. Taken together, the amino acids of the glutamate family emerge as important signaling molecules that orchestrate plant growth and development by integrating the metabolic status of the plant with environmental signals, especially in stressful conditions. This research topic collects contributions from different facets of glutamate family amino acid signaling or metabolism to bring together, and integrate in a comprehensive view the latest advances in our understanding of the multiple functions of Glu-derived amino acids in plants.


Book
Lysosomal storage diseases
Author:
ISBN: 1634847687 9781634847681 9781634846615 1634846613 Year: 2016 Publisher: New York

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Book
Amino Acids of the Glutamate Family: Functions beyond Primary Metabolism
Authors: --- --- ---
Year: 2016 Publisher: Frontiers Media SA

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The life of proteins starts and ends as amino acids. In addition to the primary function as protein building blocks, amino acids serve multiple other purposes to make a plant's life worth living. This is true especially for the amino acids of the glutamate family, namely glutamate (Glu), glutamine (Gln), proline (Pro) and arginine (Arg), as well as the product of Glu decarboxylation, ?-aminobutyric acid (GABA). Synthesis, accumulation, interconversion and degradation of these five compounds contribute in many ways to the regulation of plant development and to responses to environmental challenges. Glu and Gln hold key positions as entry points and master regulators of nitrogen metabolism in plants, and have a pivotal role in the regulatory interplay between carbon and nitrogen metabolism. Pro and GABA are among the best-studied compatible osmolytes that accumulate in response to water deficit, yet the full range of protective functions is still to be revealed. Arg, with its exceptionally high nitrogen-to-carbon ratio, has long been recognized as a major storage form of organic nitrogen. Most of the enzymes involved in metabolism of the amino acids of the glutamate family in plants have been identified or can be predicted according to similarity with animal or microbial homologues. However, for some of these enzymes the detailed biochemical properties still remain to be determined in order to understand activities in vivo. Additionally, uncertainties regarding the subcellular localization of proteins and especially the lack of knowledge about intracellular transport proteins leave significant gaps in our understanding of the metabolic network connecting Glu, Gln, Pro, GABA and Arg. While anabolic reactions are distributed between the cytosol and chloroplasts, catabolism of the amino acids of the glutamate family takes place in mitochondria and has been implicated in fueling energy-demanding physiological processes such as root elongation, recovery from stress, bolting and pollen tube elongation. Exceeding the metabolic functions, the amino acids of the glutamate family were recently identified as important signaling molecules in plants. Extracellular Glu, GABA and a range of other metabolites trigger responses in plant cells that resemble the actions of Glu and GABA as neurotransmitters in animals. Plant homologues of the Glu-gated ion channels from mammals and protein kinase signaling cascades have been implicated in these responses. Pollen tube growth and guidance depend on GABA signaling and the root architecture is specifically regulated by Glu. GABA and Pro signaling or metabolism were shown to contribute to the orchestration of defense and programmed cell death in response to pathogen attacks. Pro signaling was additionally proposed to regulate developmental processes and especially sexual reproduction. Arg is tightly linked to nitric oxide (NO) production and signaling in plants, although Arg-dependent NO-synthases could still not be identified. Potentially Arg-derived polyamines constitute the missing link between Arg and NO signaling in response to stress. Taken together, the amino acids of the glutamate family emerge as important signaling molecules that orchestrate plant growth and development by integrating the metabolic status of the plant with environmental signals, especially in stressful conditions. This research topic collects contributions from different facets of glutamate family amino acid signaling or metabolism to bring together, and integrate in a comprehensive view the latest advances in our understanding of the multiple functions of Glu-derived amino acids in plants.


Book
Amino Acids of the Glutamate Family: Functions beyond Primary Metabolism
Authors: --- --- ---
Year: 2016 Publisher: Frontiers Media SA

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Abstract

The life of proteins starts and ends as amino acids. In addition to the primary function as protein building blocks, amino acids serve multiple other purposes to make a plant's life worth living. This is true especially for the amino acids of the glutamate family, namely glutamate (Glu), glutamine (Gln), proline (Pro) and arginine (Arg), as well as the product of Glu decarboxylation, ?-aminobutyric acid (GABA). Synthesis, accumulation, interconversion and degradation of these five compounds contribute in many ways to the regulation of plant development and to responses to environmental challenges. Glu and Gln hold key positions as entry points and master regulators of nitrogen metabolism in plants, and have a pivotal role in the regulatory interplay between carbon and nitrogen metabolism. Pro and GABA are among the best-studied compatible osmolytes that accumulate in response to water deficit, yet the full range of protective functions is still to be revealed. Arg, with its exceptionally high nitrogen-to-carbon ratio, has long been recognized as a major storage form of organic nitrogen. Most of the enzymes involved in metabolism of the amino acids of the glutamate family in plants have been identified or can be predicted according to similarity with animal or microbial homologues. However, for some of these enzymes the detailed biochemical properties still remain to be determined in order to understand activities in vivo. Additionally, uncertainties regarding the subcellular localization of proteins and especially the lack of knowledge about intracellular transport proteins leave significant gaps in our understanding of the metabolic network connecting Glu, Gln, Pro, GABA and Arg. While anabolic reactions are distributed between the cytosol and chloroplasts, catabolism of the amino acids of the glutamate family takes place in mitochondria and has been implicated in fueling energy-demanding physiological processes such as root elongation, recovery from stress, bolting and pollen tube elongation. Exceeding the metabolic functions, the amino acids of the glutamate family were recently identified as important signaling molecules in plants. Extracellular Glu, GABA and a range of other metabolites trigger responses in plant cells that resemble the actions of Glu and GABA as neurotransmitters in animals. Plant homologues of the Glu-gated ion channels from mammals and protein kinase signaling cascades have been implicated in these responses. Pollen tube growth and guidance depend on GABA signaling and the root architecture is specifically regulated by Glu. GABA and Pro signaling or metabolism were shown to contribute to the orchestration of defense and programmed cell death in response to pathogen attacks. Pro signaling was additionally proposed to regulate developmental processes and especially sexual reproduction. Arg is tightly linked to nitric oxide (NO) production and signaling in plants, although Arg-dependent NO-synthases could still not be identified. Potentially Arg-derived polyamines constitute the missing link between Arg and NO signaling in response to stress. Taken together, the amino acids of the glutamate family emerge as important signaling molecules that orchestrate plant growth and development by integrating the metabolic status of the plant with environmental signals, especially in stressful conditions. This research topic collects contributions from different facets of glutamate family amino acid signaling or metabolism to bring together, and integrate in a comprehensive view the latest advances in our understanding of the multiple functions of Glu-derived amino acids in plants.


Periodical
Synthetic and systems biotechnology.
ISSN: 2405805X Year: 2016 Publisher: [China] : KeAi Communications Co.,


Book
Monoamine oxidase inhibitors
Author:
ISBN: 1634840216 9781634840217 9781634836005 Year: 2016 Publisher: New York

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Book
Quantified : biosensing technologies in everyday life
Author:
ISBN: 9780262034173 0262034174 9780262528757 0262528754 9780262334549 0262334542 9780262334532 0262334534 0262334550 9780262334556 Year: 2016 Publisher: Cambridge, Massachusetts London, England The MIT Press

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Today anyone can purchase technology that can track, quantify, and measure the body and its environment. Wearable or portable sensors detect heart rates, glucose levels, steps taken, water quality, genomes, and microbiomes, and turn them into electronic data. Is this phenomenon empowering, or a new form of social control? Who volunteers to enumerate bodily experiences, and who is forced to do so? Who interprets the resulting data? How does all this affect the relationship between medical practice and self care, between scientific and lay knowledge? Quantified examines these and other issues that arise when biosensing technologies become part of everyday life. The book offers a range of perspectives, with views from the social sciences, cultural studies, journalism, industry, and the nonprofit world. The contributors consider data, personhood, and the urge to self-quantify; legal, commercial, and medical issues, including privacy, the outsourcing of medical advice, and self-tracking as a "paraclinical" practice; and technical concerns, including interoperability, sociotechnical calibration, alternative views of data, and new space for design.

Keywords

Biosensors. --- Medical instruments and apparatus. --- Biosensing Techniques. --- Monitoring, Physiologic --- Confidentiality. --- #SBIB:316.334.3M30 --- #SBIB:316.334.3M50 --- #SBIB:316.334.3M40 --- Confidential Information --- Secrecy --- Patient Data Privacy --- Privacy of Patient Data --- Privileged Communication --- Communication, Privileged --- Communications, Privileged --- Data Privacy, Patient --- Information, Confidential --- Privacy, Patient Data --- Privileged Communications --- Duty to Warn --- Privacy --- Disclosure --- Anonymous Testing --- Parental Notification --- Biosensing Technics --- Bioprobes --- Biosensors --- Electrodes, Enzyme --- Bioprobe --- Biosensing Technic --- Biosensing Technique --- Biosensor --- Electrode, Enzyme --- Enzyme Electrode --- Enzyme Electrodes --- Technic, Biosensing --- Technics, Biosensing --- Technique, Biosensing --- Techniques, Biosensing --- Microchemistry --- Apparatus, Medical --- Instruments, Medical --- Medical apparatus --- Medical devices --- Medical products --- Medicine --- Biomedical engineering --- Medical supplies --- Scientific apparatus and instruments --- Biodetectors --- Biological detectors --- Biological sensors --- Biomedical detectors --- Biomedical sensors --- Detectors --- Medical instruments and apparatus --- Physiological apparatus --- trends. --- Medische sociologie: gezondheidsgedrag --- Organisatie van de gezondheidszorg: algemeen, beleid --- Medische sociologie: zorgenverstrekkers, relatie met hulpvragers --- Apparatus --- Equipment and supplies --- Instruments --- Wearable Electronic Devices --- INFORMATION SCIENCE/Communications & Telecommunications --- INFORMATION SCIENCE/General --- COMPUTER SCIENCE/Human Computer Interaction --- Biosensing Techniques --- Confidentiality --- trends

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