krainaksiazek design and development of novel anticoagulant agents 20124094
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Novel syntheses of the benzoquinones Idebenone and CoQ10 LAP Lambert Academic Publishing
Książki / Literatura obcojęzyczna
The topic of this project is related to the investigation, design and development of novel synthetic methods and pathways to natural antioxidants and their synthetic analogues that can be utilized as pharmaceuticals, nutraceuticals and preservation agents for food and feed, particularly marine lipids. Distinctive interest is paid to the development and exploration of phenolic and benzoquinone class of compounds such as coenzyme Q10 (CoQ10) and Idebenol. Focal point is the development of practical, efficient, and cost-effective synthetic methods and pathways that will employ cheap and readily available materials, and "green" conditions and reagents. A novel total synthesis to Idebenone is concluded while the development of a synthetic path leading to CoQ10 has also been explored. Among the deliverables are: a) a novel green bromination protocol for activated arenes b) an oxidation protocol leading to two versatile intermediates c) a purification protocol of Heck coupling post-reaction mixtures for transition metal catalyst based on organic solvent nanofiltration and d) a palladium catalyzed Heck coupling protocol performed under microwave irradiation.
Cancer Chemoprevention Springer, Berlin
Książki / Literatura obcojęzyczna
A comprehensive reference survey on the identification and development of promising cancer chemopreventive agents that will help stimulate further novel research and new approvable drugs. For each agent, the authors review the relevant mechanisms of action, the criteria for populations benefiting from intervention, the safety and pharmacodynamics, clinical study design emphasizing the use of precancers, and early associated cellular and molecular biomarkers of carcinogenesis. The pharmacologic and/or mechanistic classes discussed range from antimutagens, antiinflammatories, and the nuclear receptor superfamily, to signal transduction modulators, antioxidants, vitamins, and minerals. The overall focus is on molecular targets and mechanisms. A second volume, Strategies in Chemoprevention, describes the exciting methodologies that will accelerate progress in this field and discusses the state of clinical development of chemoprevention in the various human cancer target organs.Much progress has been made in discovering and developing agents that have promise, or have already been successfully used, to treat precancerous conditions or inhibit carcinogenesis. In Cancer Chemoprevention, Volume 1: Promising Cancer Chemopreventive Agents, leading researchers in the discovery and development of chemopreventives comprehensively survey all aspects of these emerging therapeutics. For each agent, the authors review the relevant mechanisms of action, the criteria for populations benefiting from intervention, the safety and pharmacodynamics, clinical study design emphasizing the use of precancers, and early associated cellular and molecular biomarkers of carcinogenesis. The pharmacologic and/or mechanistic classes discussed range from antimutagens, antiinflammatories, and the nuclear receptor superfamily, to signal transduction modulators, antioxidants, vitamins, and minerals. The classes vary widely in terms of their stages of development as chemopreventives and include both extensively studied groups and those with recently identified potential based on such mechanistic data as protein kinase inhibition. Attention is also devoted to nutriceuticals (food-derived agents) because of their high promise for prevention in healthy populations. The overall focus is on molecular targets and mechanisms. A second volume, Strategies for Cancer Chemoprevention, describes the exciting methodologies that are accelerating progress in this field and discusses the state of clinical development of chemoprevention in the various human cancer target organs.§Up-to-date and highly practical, Cancer Chemoprevention, Volumes 1 & 2, offer oncologists, pharmacologists, medicinal chemists, and toxicologists a comprehensive reference survey on the identification of promising cancer chemopreventive agents that will help stimulate further research and the development of novel approvable drugs.
Lasso Peptides, 1 Springer, Berlin
Książki / Literatura obcojęzyczna
Lasso peptides form a growing family of fascinating ribosomally-synthesized and post-translationally modified peptides produced by bacteria. They contain 15 to 24 residues and share a unique interlocked topology that involves an N-terminal 7 to 9-residue macrolactam ring where the C-terminal tail is threaded and irreversibly trapped. The ring results from the condensation of the N-terminal amino group with a side-chain carboxylate of a glutamate at position 8 or 9, or an aspartate at position 7, 8 or 9. The trapping of the tail involves bulky amino acids located in the tail below and above the ring and/or disulfide bridges connecting the ring and the tail. Lasso peptides are subdivided into three subtypes depending on the absence (class II) or presence of one (class III) or two (class I) disulfide bridges. The lasso topology results in highly compact structures that give to lasso peptides an extraordinary stability towards both protease degradation and denaturing conditions. Lasso peptides are generally receptor antagonists, enzyme inhibitors and/or antibacterial or antiviral (anti-HIV) agents. The lasso scaffold and the associated biological activities shown by lasso peptides on different key targets make them promising molecules with high therapeutic potential. Their application in drug design has been exemplified by the development of an integrin antagonist based on a lasso peptide scaffold. The biosynthesis machinery of lasso peptides is therefore of high biotechnological interest, especially since such highly compact and stable structures have to date revealed inaccessible by peptide synthesis. Lasso peptides are produced from a linear precursor LasA, which undergoes a maturation process involving several steps, in particular cleavage of the leader peptide and cyclization. The post-translational modifications are ensured by a dedicated enzymatic machinery, which is composed of an ATP-dependent cysteine protease (LasB) and a lactam synthetase (LasC) that form an enzymatic complex called lasso synthetase. Microcin J25, produced by Escherichia coli AY25, is the archetype of lasso peptides and the most extensively studied. To date only around forty lasso peptides have been isolated, but genome mining approaches have revealed that they are widely distributed among Proteobacteria and Actinobacteria, particularly in Streptomyces, making available a rich resource of novel lasso peptides and enzyme machineries towards lasso topologies.§
Sklepy zlokalizowane w miastach: Warszawa, Kraków, Łódź, Wrocław, Poznań, Gdańsk, Szczecin, Bydgoszcz, Lublin, Katowice
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t1=0.023, t2=0, t3=0, t4=0, t=0.023