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Simon Boecker, Stefan Grätz, Dennis Kerwat, Lutz Adam, David Schirmer, Lennart Richter, Tabea Schütze, Daniel Petras, Roderich D Süssmuth, Vera Meyer
Background: Fungal cyclodepsipeptides (CDPs) are non-ribosomally synthesized peptides produced by a variety of filamentous fungi and are of interest to the pharmaceutical industry due to their anticancer, antimicrobial and anthelmintic bioactivities. However, both chemical synthesis and isolation of CDPs from their natural producers are limited due to high costs and comparatively low yields. These challenges might be overcome by heterologous expression of the respective CDP-synthesizing genes in a suitable fungal host...
2018: Fungal Biology and Biotechnology
Muriel Gondry, Isabelle B Jacques, Robert Thai, Morgan Babin, Nicolas Canu, Jérôme Seguin, Pascal Belin, Jean-Luc Pernodet, Mireille Moutiez
Cyclodipeptide synthases (CDPSs) use as substrates two amino acids activated as aminoacyl-tRNAs to synthesize cyclodipeptides in secondary metabolites biosynthetic pathways. Since the first description of a CDPS in 2002, the number of putative CDPSs in databases has increased exponentially, reaching around 800 in June 2017. They are likely to be involved in numerous biosynthetic pathways but the diversity of their products is still under-explored. Here, we describe the activity of 32 new CDPSs, bringing the number of experimentally characterized CDPSs to about 100...
2018: Frontiers in Microbiology
Leon Maser, Jan Herritsch, Robert Langer
The reactivity patterns of carbodiphosphoranes (CDPs) as ligands are much less explored than those of isoelectronic analogues. In the current manuscript, we investigate the reactivity of the carbodiphosphorane-based PCP nickel(ii) pincer complex [({dppm}2 C)NiCl]Cl (1) towards acids and bases, calculate proton affinities, analyse the bonding situation and tautomeric forms with the aim to evaluate whether CDPs can potentially act as cooperative ligands in catalysis (dppm = 1,1-bis(diphenylphosphino)methane)...
February 22, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Xiaohan Wang, Xiao Gong, Peng Li, Daowan Lai, Ligang Zhou
Cyclic depsipeptides (CDPs) are cyclopeptides in which amide groups are replaced by corresponding lactone bonds due to the presence of a hydroxylated carboxylic acid in the peptide structure. These peptides sometimes display additional chemical modifications, including unusual amino acid residues in their structures. This review highlights the occurrence, structures and biological activities of the fungal CDPs reported until October 2017. About 352 fungal CDPs belonging to the groups of cyclic tri-, tetra-, penta-, hexa-, hepta-, octa-, nona-, deca-, and tridecadepsipeptides have been isolated from fungi...
January 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Enrique Martínez-Carranza, Gabriel Y Ponce-Soto, Alma L Díaz-Pérez, Erasmo Cadenas, Valeria Souza, Jesús Campos-García
The Cuatro Ciénegas Basin (CCB) within the Chihuahuan Desert in México is an extremely oligotrophic oasis with negligible phosphorous levels, described as a hot spot of biodiversity, not only in stromatolites and microbial mats, but also in living forms in general. The microorganisms possess the capability to produce a wide variety of virulence factors, antibiotics, and quorum-sensing (QS) crosstalk signals such as non-ribosomal cyclodipeptides (CDPs) which enables them to colonize diverse ecological niches...
November 11, 2017: Extremophiles: Life Under Extreme Conditions
Nobuyuki Onai, Jumpei Asano, Rumiko Kurosaki-Nakamura, Shoko Kuroda, Toshiaki Ohteki
The basic helix-loop-helix transcription factor E2-2 is essential for the development of plasmacytoid dendritic cells (pDCs) but not conventional DCs (cDCs). Here, we generated E2-2 reporter mice and demonstrated that an E2-2high fraction among common DC progenitors (CDPs), which are a major source of pDCs and cDCs in the steady state, strictly gave rise to pDCs in the presence of Flt3 ligand ex vivo or in the secondary lymphoid organs when transferred in vivo. However, in the small intestine, some of these E2-2high progenitors differentiated into cDCs that produced retinoic acid...
November 2, 2017: International Immunology
Awdhesh Kumar Mishra, Jaehyuk Choi, Seong-Jin Choi, Kwang-Hyun Baek
Cyclodipeptides (CDP) represent a diverse family of small, highly stable, cyclic peptides that are produced as secondary functional metabolites or side products of protein metabolism by bacteria, fungi, and animals. They are widespread in nature, and exhibit a broad variety of biological and pharmacological activities. CDP synthases (CDPSs) and non-ribosomal peptide synthetases (NRPSs) catalyze the biosynthesis of the CDP core structure, which is further modified by tailoring enzymes often associated with CDP biosynthetic gene clusters...
October 23, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Kirsten Brockmeyer, Shu-Ming Li
Expression of a cyclodipeptide synthase gene from Nocardiopsis prasina (CDPS-Np) in Escherichia coli resulted in the formation of cyclo-(l-Tyr-l-Tyr) (1) as the minor and cyclo-(l-Tyr-l-Phe) (2) as the major products. Site-directed mutagenesis revealed a strong influence on product accumulation of the amino acid residues in pocket P1. An 8-fold increase in product formation for 1 and 10-fold for 2 were detected in the double mutant T82V_Y196F compared with the wild type.
October 24, 2017: Journal of Natural Products
Jerry Nedelman, Roland Fisch, Ke Hu, Ines Paule, Jocelyn Zhou
BACKGROUND AND OBJECTIVE: Pasireotide (SOM230, Signifor(®)) is a somatostatin analog approved in a subcutaneous formulation for the treatment of Cushing's disease. This analysis characterizes the population pharmacokinetics (PopPK) of subcutaneous pasireotide jointly in healthy volunteers (HVs) and Cushing's disease patients (CDPs), evaluating the effects of age, body size, and population on pasireotide pharmacokinetics. METHODS: The analysis dataset included five phase I studies and one each from phase II and phase III...
October 14, 2017: Clinical Pharmacokinetics
Zhanghui Wang, Peibin Zhang, Fan Hu, Yifan Zhao, Liping Zhu
Organic micropollutants in aquatic environment such as plasticizer, pesticide and pharmaceuticals, have posed a serious threat to human health and are emerging as a great challenge to humanity. Traditional water treatment techniques fail to achieve high removal efficiency for low concentration of organic micropollutants. Here we demonstrate a water-insoluble crosslinked β-cyclodextrin (β-CD) polymer able to remove a broad-spectrum of organic micropollutants from water by rapid adsorption. A family of β-CD polymers (β-CDPs) were synthesized by nucleophilic aromatic substitution of β-CD hydroxyl groups and 4,4'-difluorodiphenylsulfone...
December 1, 2017: Carbohydrate Polymers
Lawrence Paszat, Rinku Sutradhar, Mary Ann O'Brien, Aisha Lofters, Andrew Pinto, Peter Selby, Nancy Baxter, Peter D Donnelly, Regina Elliott, Richard H Glazier, Robert Kyle, Donna Manca, Mary-Anne Pietrusiak, Linda Rabeneck, Nicolette Sopcak, Jill Tinmouth, Becky Wall, Eva Grunfeld
BACKGROUND: The Building on Existing Tools to Improve Chronic Disease Prevention and Screening (BETTER) cluster randomized trial in primary care settings demonstrated a 30% improvement in adherence to evidence-based Chronic Disease Prevention and Screening (CDPS) activities. CDPS activities included healthy activities, lifestyle modifications, and screening tests. We present a protocol for the adaptation of BETTER to a public health setting, and testing the adaptation in a cluster randomized trial (BETTER HEALTH: Durham) among low income neighbourhoods in Durham Region, Ontario (Canada)...
September 29, 2017: BMC Public Health
Shivaprasad Manchineella, N Arul Murugan, Thimmaiah Govindaraju
Ambidextrous supergelators are developed through structure-gelation screening of rationally designed cyclic dipeptides (CDPs). The organo- and hydrogels of CDPs were thoroughly characterized by their minimal gelation concentration (MGC) for organic and aqueous solvents, thermal stability (Tg), and viscoelastic properties. Intermolecular hydrogen bonding, the major driving force for gelation was evaluated using temperature-dependent nuclear magnetic resonance (NMR) spectroscopy. The contribution of attractive van der Waals interaction of tBoc group in driving CDP gelation was ascertained using β-cyclodextrin (β-CD)-adamantane carboxylic acid (AC)-based host-guest gelation and (1)H NMR studies...
September 14, 2017: Biomacromolecules
Donyez Frikha Dammak, Ziad Zarai, Soumaya Najah, Rayed Abdennabi, Lassaad Belbahri, Mostafa E Rateb, Hafedh Mejdoub, Sami Maalej
This study has focused on the isolation of twenty-three halophilic actinomycetes from two ponds of different salinity and the evaluation of their ability to exert an antimicrobial activity against both their competitors and several other pathogens. From the 23 isolates, 18 strains showed antagonistic activity, while 19 showed activities against one or more of the seven pathogen strains tested. Six strains exhibited consistent antibacterial activity against Gram-negative and Gram-positive pathogens characterized at the physiological and molecular levels...
2017: BioMed Research International
Seong Woo Noh, Rira Seo, Jung-Kwon Park, Md Maniruzzaman Manir, Kyungseok Park, Mee Kyung Sang, Surk-Sik Moon, Ho Won Jung
Cyclic dipeptides (CDPs) are one of the simplest compounds produced by living organisms. Plant-growth promoting rhizobacteria (PGPRs) also produce CDPs that can induce disease resistance. Bacillus vallismortis strain BS07 producing various CDPs has been evaluated as a potential biocontrol agent against multiple plant pathogens in chili pepper. However, plant signal pathway triggered by CDPs has not been fully elucidated yet. Here we introduce four CDPs, cyclo(Gly-L-Pro) previously identified from Aspergillus sp...
August 2017: Plant Pathology Journal
Lior Aram, Keren Yacobi-Sharon, Eli Arama
No abstract text is available yet for this article.
August 2017: Cell Death and Differentiation
Susannah Sadler, Jon Tosh, Rebekah Pennington, Andrew Rawdin, Hazel Squires, Carmen Romero, Alastair Fischer, James Chilcott
BACKGROUND: Prevention of sexually transmitted infection (STI) incidence in England is a high priority, particularly among young people, men who have sex with men (MSM) and black ethnic minorities. An economic evaluation of condom distribution programmes (CDPs) to reduce STI transmission is presented. METHODS: An economic model using a Bernoulli process estimated the number of people acquiring an STI as a function of its prevalence, transmission rate, condom use, condom failure rate and number of sexual contacts...
July 5, 2017: Journal of Epidemiology and Community Health
Tam Dang, Roderich D Süssmuth
The need for new drugs for the treatment of various diseases is enormous. From the previous century until the present, numerous peptide and peptide-derived natural products have been isolated from bacteria and fungi. Hence, microorganisms play a pivotal role as sources for novel drugs with an emphasis on anti-infective agents. Various disciplines from biology, chemistry, and medicine are involved in early stages of the search for peptide natural products including taxonomy, microbiology, bioanalytics, bioinformatics, and medicinal chemistry...
June 26, 2017: Accounts of Chemical Research
Laura Hernández-Padilla, Dolores Vázquez-Rivera, Luis A Sánchez-Briones, Alma L Díaz-Pérez, José Moreno-Rodríguez, Mario A Moreno-Eutimio, Victor Meza-Carmen, Homero Reyes-De la Cruz, Jesús Campos-García
Pseudomonas aeruginosa PAO1, a potential pathogen of plants and animals, produces the cyclodipeptides cyclo(l-Pro-l-Tyr), cyclo(l-Pro-l-Phe), and cyclo(l-Pro-l-Val) (PAO1-CDPs), whose effects have been implicated in inhibition of human tumor cell line proliferation. Our purpose was to investigate in depth in the mechanisms of HeLa cell proliferation inhibition by the PAO1-CDPs. The results indicate that PAO1-CDPs, both purified individually and in mixtures, inhibited HeLa cell proliferation by arresting the cell cycle at the G0-G1 transition...
June 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ginetta Salvalaggio, Christopher Meaney, Rahim Moineddin, Eva Grunfeld, Donna Manca
BACKGROUND: Primary care plays a pivotal role in the provision of both mental health care and chronic disease prevention and screening (CDPS). Unfortunately, moderate mental illness (MMI) is associated with poorer general health outcomes. Part of this burden of illness may be due to reduced CDPS uptake. The Building on the Existing Tools to Improve Chronic Disease Prevention in Primary Care (BETTER) trial recruited 777 participants ages 40-65 from 32 family practice panels, of whom 135 (18...
June 17, 2017: BMC Family Practice
Mario Martin, Javier Béjar, Gennaro Esposito, Diógenes Chávez, Enrique Contreras-Hernández, Silvio Glusman, Ulises Cortés, Pablo Rudomín
In a previous study we developed a Machine Learning procedure for the automatic identification and classification of spontaneous cord dorsum potentials (CDPs). This study further supported the proposal that in the anesthetized cat, the spontaneous CDPs recorded from different lumbar spinal segments are generated by a distributed network of dorsal horn neurons with structured (non-random) patterns of functional connectivity and that these configurations can be changed to other non-random and stable configurations after the noceptive stimulation produced by the intradermic injection of capsaicin in the anesthetized cat...
2017: Frontiers in Computational Neuroscience
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