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Steroids --- Acetogenins

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This thesis reports studies on the substrate specificity of crucial ketosynthase (KS) domains from trans-AT Polyketide Synthases (PKSs). Using a combination of electrospray ionisation-mass spectrometry (ESI-MS) and simple N-acetyl cysteamine (SNAC) substrate mimics, Matthew Jenner has successfully studied the specificity of a range of KS domains from the bacillaene and psymberin PKSs with regard to the initial acylation step of KS-catalysis. The findings in this thesis provide important insights into mechanisms of KS specificity and show that mutagenesis can be used to expand the repertoire of acceptable substrates for future PKS engineering. The documentation of this research is a useful reference and guideline for students starting a PhD in this field.

Analytical Chemistry --- Chemistry --- Physical Sciences & Mathematics --- Polyketides --- Mass spectrometry. --- Spectra. --- Mass spectra --- Mass spectrograph --- Mass spectroscopy --- Mass spectrum analysis --- Acetogenins --- Mass (Physics) --- Nuclear spectroscopy --- Spectrum analysis --- Ketenes --- Polymers --- Enzymes. --- Biochemical engineering. --- Biochemistry. --- Mass Spectrometry. --- Enzymology. --- Biochemical Engineering. --- Medical Biochemistry. --- Biological chemistry --- Chemical composition of organisms --- Organisms --- Physiological chemistry --- Biology --- Medical sciences --- Bio-process engineering --- Bioprocess engineering --- Biochemistry --- Biotechnology --- Chemical engineering --- Biocatalysts --- Ferments --- Soluble ferments --- Catalysts --- Proteins --- Enzymology --- Composition --- Medical biochemistry. --- Medical biochemistry --- Pathobiochemistry --- Pathological biochemistry --- Pathology --- Enzymes

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Microbial natural products have been an important traditional source of valuable antibiotics and other drugs but interest in them waned in the 1990s when big pharma decided that their discovery was no longer cost-effective and concentrated instead on synthetic chemistry as a source of novel compounds, often with disappointing results. Moreover understanding the biosynthesis of complex natural products was frustratingly difficult. With the development of molecular genetic methods to isolate and manipulate the complex microbial enzymes that make natural products, unexpected chemistry has been

Anti-Bacterial agents -- Biosynthesis. --- Biological products -- Biosynthesis. --- Carbohydrates -- Biosynthesis. --- Peptide Biosynthesis --- Biological Products --- Anti-Bacterial Agents --- Polyketide Synthases --- Enzymes --- Carbohydrates --- Complex Mixtures --- Enzymes and Coenzymes --- Anti-Infective Agents --- Biochemical Processes --- Multienzyme Complexes --- Metabolism --- Chemicals and Drugs --- Carbon-Carbon Ligases --- Biochemical Phenomena --- Ligases --- Therapeutic Uses --- Metabolic Phenomena --- Chemical Processes --- Phenomena and Processes --- Chemical Phenomena --- Pharmacologic Actions --- Chemical Actions and Uses --- Biosynthesis. --- Peptides --- Polyketides --- Synthesis. --- Microbial biotechnology. --- Carbs (Carbohydrates) --- Peptide synthesis --- Acetogenins --- Biological synthesis --- Synthesis, Biological --- Microorganisms --- Biotechnology --- Biomolecules --- Organic compounds --- Glycomics --- Ketenes --- Polymers --- Biochemical engineering --- Biochemistry --- Synthetic biology --- Biochemical templates --- Industrial microbiology --- Biotechnological microorganisms --- Synthesis

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The very first marine-derived anticancer drug, Cytarabine (aka Ara-C, Cytosar-U®), was approved by the FDA in 1969 for the treatment of leukemia. At the beginning of 2021, the list of approved marine-derived anticancer drugs consists of nine substances, five of which received approval within the last two years, demonstrating the rapid evolution of the field. The current book is a collection of scientific articles related to the exponentially growing field of anticancer marine compounds. These articles cover the whole field, from agents with cancer-preventive activity, to novel and previously characterized compounds with anticancer activity, both in vitro and in vivo, as well as the latest status of compounds under clinical development.

Medicine --- apoptosis --- fucoidan --- hepatocellular carcinoma --- reactive oxygen species --- 3-alkylpyridinium polymers --- nicotine --- nicotinic acetylcholine receptor --- non-small cell lung carcinoma --- melanoma --- sinulariolide --- proteomic --- mitochondria --- caspase cascade --- marine fungus --- sediment --- anthranilic acid --- Penicillium paneum --- cytotoxicity --- dibromotyrosine --- mitochondrial dysfunction --- oxidative stress --- topoisomerase --- epigonal organ --- bonnethead shark --- Jurkat --- tumor cell line --- hippuristanol --- PEL --- AP-1 --- STAT3 --- Akt --- colorectal cancer --- marine mollusc --- brominated indoles --- shrimp --- chemoprevention --- fatty acids --- carotenoids --- cancer --- nanoparticle --- osteosarcoma --- lung metastasis --- elisidepsin --- lipid rafts --- hydroxylated lipids --- fatty acid 2-hydroxylase --- cooperative binding --- membrane permeabilization --- marine organisms --- polysaccharides --- anticancer --- anticarcinogenic --- mechanisms of action --- fumigaclavine C --- anti-proliferation --- mitochondrial pathway --- anti-cancer --- anti-proliferative --- carotenoid --- cell cycle arrest --- fucoxanthin --- azoxymethane --- bioactive natural product --- isatin --- in vivo model --- Marthasterias glacialis L. --- palmitic acid --- ER-stress --- CHOP --- Antibody Drug Conjugates (ADCs) --- marine antitumor agents --- clinical trials --- approved antitumor agents --- AD0157 --- angiogenesis --- marine drug --- pyrrolidinedione --- secondary metabolites --- cancer preventive --- chemopreventive --- trabectedin --- plitidepsin --- tumor-associated macrophages --- tumor microenvironment --- preclinical --- anticancer immunity --- antiangiogenesis --- fascaplysin --- cyclin-dependent kinase --- small cell lung cancer --- camptothecin --- poly(ADP-ribose)-polymerase inhibitor --- breast cancer --- seaweed --- therapeutic compounds --- autophagy --- marine drugs --- autophagy inhibitors --- autophagy inducers --- macrolide --- programmed cell death --- energy stress --- araguspongine C --- c-Met --- HER2 --- gemcitabine --- pazopanib --- phase I --- safety --- soft tissue sarcoma --- pachastrissamine --- jaspine B --- carbocyclic analogue --- sphingosine kinase inhibitor --- molecular modeling --- ET-743 --- DNA minor groove binder --- chemotherapy --- bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM) --- anti-metastatic activity --- cell adhesion --- β1-integrin --- FAK --- BEL-7402 cell --- triterpene glycosides --- sea cucumbers --- antitumor activities --- arrest of cell cycle --- antibacterial --- marangucyclines --- deep-sea --- Streptomyces sp. SCSIO 11594 --- LS-1 --- SNU-C5/5-FU --- TGF-β signaling --- carcinoembryonic antigen --- kalkitoxin --- Moorea producens --- mitochondria toxin --- VEGF --- angiogenesis inhibitor --- hypoxia-inducible factor-1 --- HIF-1 --- Lyngbya majuscula --- marine metabolites --- SZ-685C --- nonfunctioning pituitary adenomas --- Ecklonia cava --- phlorotannins --- dieckol --- migration --- sipholenol A --- ABC transporter --- multidrug resistance --- P-gp/ABCB1 --- BCRP/ABCG2 --- MRP1/ABCC1 --- marine natural products --- glioblastoma --- xyloketal B --- proliferation --- TRPM7 --- marine compound --- ribosomal protein genes --- snoRNA --- FAU --- RPS30 --- SNORA62 --- evolution --- Porifera --- Penicillium brevicompactum --- Brevianamide --- Mycochromenic acid derivative --- antifouling --- Caribbean sponge --- plakortide --- endoperoxide --- leukemia --- multi-drug resistant leukemia --- Sarcophyton ehrenbergi --- soft coral --- terpenes --- cembranoids --- cytotoxic activity --- molecular docking --- uveal melanoma --- virtual screening --- Topo I inhibitor --- low toxic --- natural product --- Ulva fasciata --- selenium-containing polysaccharide-protein complex --- pseudopterosin --- NF-κB --- p65 --- inflammation --- cytokine release --- IL-6 --- TNFα --- MCP-1 --- glucocorticoid receptor --- paulomycins --- Micromonospora --- antitumor --- Cantabrian Sea-derived actinobacteria --- puupehenones --- sponges --- antiangiogenic --- antitumoral --- porifera/sponge --- cancer genes --- molecular oncology --- bromophenol --- molecular mechanisms --- cell cycle --- PI3K/Akt --- p38/ERK --- ROS --- human lung cancer --- glycosaminoglycans --- antiproliferative --- heparan sulphate --- gliotoxin --- NSCLC --- adriamycin resistance --- Sepia ink polysaccharides --- antitumour --- chemosensitization --- anticoagulation --- sea anemone --- drug discovery --- endothelial cells --- RGD motif --- kunitz type inhibitor --- prostate cancer --- antioxidant --- natural marine compounds --- marine biotechnology --- microalgae --- marine sponges --- Aeroplysinin --- Isofistularin --- pheochromocytoma and paraganglioma --- metastasis --- cancer progression --- cell adhesion molecules --- integrin β1 --- hypoxia --- phycocyanin --- non-small cell lung cancer --- NF-κB signaling --- marine-derived drugs --- bioanalysis --- chromatography --- manzamine A --- epithelial-mesenchymal transition --- lung cancer --- circulating tumor cells --- signal transduction --- cisplatin --- Lampetra morii --- buccal gland --- cystatin F --- anti-angiogenesis --- cystatin superfamily --- Antimicrobial peptide (AMP) --- Tilapia piscidin 4 (TP4) --- non-small cell lung cancer (NSCLC) --- itampolin A --- FBDD --- p38α --- novel inhibitor --- tetracenomycin X --- cyclin D1 --- proteasomal degradation --- p38 --- c-JUN --- λ-carrageenan --- heparanase --- anticoagulant --- depolymerisation --- cell migration --- Aspergillus --- naphthopyrones --- endophytic fungus --- Leathesia nana --- mangrove-derived actinomycete --- ansamycins --- divergolides --- apoptosis-inducing activity --- actinomycin --- EMT --- invasion --- low molecular weight fucoidan extract --- N-Ras --- neuroblastoma-rat sarcoma --- Cancer --- programmed cell death-ligand 1 --- programmed cell death-ligand 2 --- human sarcoma cell line (HT1080 cells) --- human normal diploid fibroblast (TIG-1 cells) --- chimera --- chemical conjugation --- anticancer agent --- hybridization --- α9-nicotinic acetylcholine receptors (nAChRs) --- breast cancer cells --- αO-conotoxin GeXIVA --- targeted therapy --- gorgonian --- Leptogorgia --- humulane sesquiterpenoids --- anticancer activity --- 12-deacetyl-12-epi-scalaradial --- HeLa cells --- Nur77 --- MAPK/ERK pathway --- Mycalin A --- C15 acetogenins --- synthetic analogues --- antiproliferative activity --- A375 and HeLa cell lines --- polyoxygenated steroids --- sponge --- Haliclona gracilis --- Thalassia testudinum --- thalassiolin B --- polyphenols --- CYP1A1 --- benzo[a]pyrene --- JNK1/2 --- natural products --- synergism --- A549 cells --- cytoskeleton --- P2X7 receptor --- pollution --- anti-angiogenic --- gene expression --- HSP90 --- inhibitor