13,148 results match your criteria Bioorganic & Medicinal Chemistry Letters[Journal]


The role of the Hint1 protein in the metabolism of phosphorothioate oligonucleotides drugs and prodrugs, and the release of HS under cellular conditions.

Biochem Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz, 91-063, Poland.

Phosphorothioate oligonucleotides (PS-oligos) containing sulfur atom attached in a nonbridging position to the phosphorus atom at one or more internucleotide bond(s) are often used in medicinal applications. Their hydrolysis in cellular media proceeds mainly from the 3'-end, resulting in the appearance of nucleoside 5'-O-phosphorothioates ((d)NMPS), whose further metabolism is poorly understood. We hypothesize that the enzyme responsible for (d)NMPS catabolism could be Hint1, an enzyme that belongs to the histidine triad (HIT) superfamily and is present in all organisms. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.018DOI Listing
February 2019

Novel -alkyl Derivatives of Naringenin and Their Oximes with Antimicrobial and Anticancer Activity.

Molecules 2019 Feb 14;24(4). Epub 2019 Feb 14.

Department of Chemistry, Faculty of Biotechnology and Food Science, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland.

In our investigation, we concentrated on naringenin ()-a widely studied flavanone that occurs in citrus fruits. As a result of a reaction with a range of alkyl iodides, 7 novel -alkyl derivatives of naringenin (⁻, , ) were obtained. Another chemical modification led to 9 oximes of -alkyl naringenin derivatives (⁻, ⁻) that were never described before. Read More

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http://dx.doi.org/10.3390/molecules24040679DOI Listing
February 2019

Design and synthesis of aminothiazolyl norfloxacin analogues as potential antimicrobial agents and their biological evaluation.

Eur J Med Chem 2019 Feb 4;167:105-123. Epub 2019 Feb 4.

Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, PR China. Electronic address:

A series of aminothiazolyl norfloxacin analogues as a new type of potential antimicrobial agents were synthesized and screened for their antimicrobial activities. Most of the prepared compounds exhibited excellent inhibitory efficiencies. Especially, norfloxacin analogue II-c displayed superior antimicrobial activities against K. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.01.072DOI Listing
February 2019

Synthetic Studies toward Plumisclerin A.

Org Lett 2019 Feb 15. Epub 2019 Feb 15.

State Key Laboratory of Bioorganic and Natural Products Chemistry , Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , 345 Lingling Lu , Shanghai 200032 , China.

A concise approach to synthesize the tetracyclic framework of the marine diterpenoid plumisclerin A is described. Starting from commercially available iridoid genipin, a highly selective intermolecular Diels-Alder reaction was utilized to construct the A/B/C tricycle. Later, a four-step sequence involving stereoselective epoxidation and Dauben oxidative rearrangement was developed to introduce the requisite enone moiety. Read More

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http://pubs.acs.org/doi/10.1021/acs.orglett.9b00095
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http://dx.doi.org/10.1021/acs.orglett.9b00095DOI Listing
February 2019
1 Read

Nuclear nanomedicine using Si nanoparticles as safe and effective carriers of Re radionuclide for cancer therapy.

Sci Rep 2019 Feb 14;9(1):2017. Epub 2019 Feb 14.

MEPhI, Institute of Engineering Physics for Biomedicine (PhysBio), 115409, Moscow, Russia.

Nuclear nanomedicine, with its targeting ability and heavily loading capacity, along with its enhanced retention to avoid rapid clearance as faced with molecular radiopharmaceuticals, provides unique opportunities to treat tumors and metastasis. Despite these promises, this field has seen limited activities, primarily because of a lack of suitable nanocarriers, which are safe, excretable and have favorable pharmacokinetics to efficiently deliver and retain radionuclides in a tumor. Here, we introduce biodegradable laser-synthesized Si nanoparticles having round shape, controllable low-dispersion size, and being free of any toxic impurities, as highly suitable carriers of therapeutic Re radionuclide. Read More

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http://dx.doi.org/10.1038/s41598-018-38474-7DOI Listing
February 2019

A DFT-based study of the hydrogen-bonding interactions between myricetin and ethanol/water.

J Mol Model 2019 Feb 14;25(3):67. Epub 2019 Feb 14.

Key Laboratory of Pollinating Insect Biology, Ministry of Agriculture and Rural Affairs, Beijing, 100093, People's Republic of China.

Flavonoids are vital constituents of propolis that are responsible for its medicinal activity. Flavonoid extraction commonly employs ethanol and water as solvents. In the extraction reaction, hydrogen-bonding interactions play a crucial role. Read More

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http://dx.doi.org/10.1007/s00894-019-3940-8DOI Listing
February 2019

A Control-Theoretic Model of Atherosclerosis.

Int J Mol Sci 2019 Feb 12;20(3). Epub 2019 Feb 12.

Institute of Computing Science, Poznan University of Technology, 60-965 Poznan, Poland.

We propose a control-theoretic aggregate model of the progression of atherosclerosis plaque, a chronic inflammatory disease of the arterial wall, to study the basic features of this disease. In the model, we exploit the role of inflammation in the disease progression, and use statins-drugs commonly recommended in atherosclerosis-to control this progression. We use a logistic function to allow for constrained growth of plaque. Read More

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http://dx.doi.org/10.3390/ijms20030785DOI Listing
February 2019

Phenotypic Plasticity of Invasive Edge Glioma Stem-like Cells in Response to Ionizing Radiation.

Cell Rep 2019 Feb;26(7):1893-1905.e7

Department of Translational Molecular Pathology and Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Unresectable glioblastoma (GBM) cells in the invading tumor edge can act as seeds for recurrence. The molecular and phenotypic properties of these cells remain elusive. Here, we report that the invading edge and tumor core have two distinct types of glioma stem-like cells (GSCs) that resemble proneural (PN) and mesenchymal (MES) subtypes, respectively. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.01.076DOI Listing
February 2019
1 Read
7.207 Impact Factor

Selective recognition of c-MYC Pu22 G-quadruplex by a fluorescent probe.

Nucleic Acids Res 2019 Feb 13. Epub 2019 Feb 13.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China.

Nucleic acid mimics of fluorescent proteins can be valuable tools to locate and image functional biomolecules in cells. Stacking between the internal G-quartet, formed in the mimics, and the exogenous fluorophore probes constitutes the basis for fluorescence emission. The precision of recognition depends upon probes selectively targeting the specific G-quadruplex in the mimics. Read More

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http://dx.doi.org/10.1093/nar/gkz059DOI Listing
February 2019

Cysteine-Aminoethylation-Assisted Chemical Ubiquitination of Recombinant Histones.

J Am Chem Soc 2019 Feb 13. Epub 2019 Feb 13.

Tsinghua-Peking Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Center for Synthetic and Systems Biology, State Key Laboratory of Chemical Oncogenomics (Shenzhen), Department of Chemistry , Tsinghua University , Beijing 100084 , China.

Histone ubiquitination affects the structure and function of nucleosomes through tightly regulated dynamic reversible processes. The efficient preparation of ubiquitinated histones and their analogs is important for biochemical and biophysical studies on histone ubiquitination. Here, we report the CAACU (cysteine-aminoethylation assisted chemical ubiquitination) strategy for the efficient synthesis of ubiquitinated histone analogs. Read More

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http://dx.doi.org/10.1021/jacs.8b13213DOI Listing
February 2019

Dimethyl fumarate, a two-edged drug: Current status and future directions.

Med Res Rev 2019 Feb 12. Epub 2019 Feb 12.

Department of Development, Reproduction and Cancer, Paris Descartes University, Sorbonne Paris Cité, INSERM U1016, Cochin Institute, CARPEM, Paris, France.

Dimethyl fumarate (DMF) is a fumaric acid ester registered for the treatment of relapsing-remitting multiple sclerosis (RRMS). It induces protein succination leading to inactivation of cysteine-rich proteins. It was first shown to possess cytoprotective and antioxidant effects in noncancer models, which appeared related to the induction of the nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) pathway. Read More

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http://dx.doi.org/10.1002/med.21567DOI Listing
February 2019

Perhydrolysis in Ethereal HO Mediated by MoO(acac): Distinct Chemoselectivity between Ketones, Ketals, and Epoxides.

Org Lett 2019 Feb 12. Epub 2019 Feb 12.

State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis , Shanghai Institute of Organic Chemistry and the University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road , Shanghai 200032 , China.

Ketones, ketals, and epoxides were converted into corresponding hydroperoxides in high yields by reaction with ethereal HO in the presence of a catalytic amount of MoO(acac) with distinct (to date unattainable) chemoselectivity. Read More

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http://pubs.acs.org/doi/10.1021/acs.orglett.9b00425
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http://dx.doi.org/10.1021/acs.orglett.9b00425DOI Listing
February 2019
4 Reads

Optimization of CRISPR/Cas9 technology to knock-out genes of interest in aneuploid cell lines.

Tissue Eng Part C Methods 2019 Feb 12. Epub 2019 Feb 12.

Institute of Regenerative Medicine, Medical Research and Education Center, Moscow, Russian Federation.

Most commonly used cell lines are readily susceptible to genome editing and present a good object for cell models to establish disease-causing genes and find ways to cure diseases. However, karyotype and phenotype heterogeneity between individual cells in such cultures as well as multiplicity of target alleles make generation of desired cell lines via single-cell cloning (used for diploid cells) inapplicable. We designed and tested a simple approach for targeted genome modification of single cells in sizable cell populations, containing multiple karyotype and phenotype variants. Read More

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http://dx.doi.org/10.1089/ten.TEC.2018.0365DOI Listing
February 2019

Synthesis of nonracemic hydroxyglutamic acids.

Beilstein J Org Chem 2019 25;15:236-255. Epub 2019 Jan 25.

Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.

Glutamic acid is involved in several cellular processes though its role as the neurotransmitter is best recognized. For detailed studies of interactions with receptors a number of structural analogues of glutamic acid are required to map their active sides. This review article summarizes syntheses of nonracemic hydroxyglutamic acid analogues equipped with functional groups capable for the formation of additional hydrogen bonds, both as donors and acceptors. Read More

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http://dx.doi.org/10.3762/bjoc.15.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350885PMC
January 2019

Crystal structures of aminotransferases Aro8 and Aro9 from Candida albicans and structural insights into their properties.

J Struct Biol 2019 Feb 8. Epub 2019 Feb 8.

Department of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, Poland. Electronic address:

Aminotransferases catalyze reversibly the transamination reaction by a ping-pong bi-bi mechanism with pyridoxal 5'-phosphate (PLP) as a cofactor. Various aminotransferases acting on a range of substrates have been reported. Aromatic transaminases are able to catalyze the transamination reaction with both aromatic and acidic substrates. Read More

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http://dx.doi.org/10.1016/j.jsb.2019.02.001DOI Listing
February 2019

On-site sampling of inorganic contamination on the metal surface and analysis with capillary electrophoresis.

J Sep Sci 2019 Feb 11. Epub 2019 Feb 11.

Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, MOE Key Laboratory of Bioorganic Phosphorus Chemistry &Chemical Biology, Tsinghua University, Beijing, China.

Pipes are the primary structural elements used for transporting fluid in various industries. The most common damage mechanism is corrosion, which occurs in pipes surface of turbine. The corrosive compounds for pipes are inorganic ion (Na , Cl , NH , NO , et al. Read More

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http://dx.doi.org/10.1002/jssc.201800916DOI Listing
February 2019

Selective reduction of 1,5-diazacyclooctatetraenes: synthesis and structures of aromatic diazacyclooctatetraenyl dianions and a 2,6-bipyrrolinyl dianionic Co(ii) complex.

Chem Commun (Camb) 2019 Feb 11. Epub 2019 Feb 11.

Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China.

Selective reduction of 1,5-diazacyclooctatetraenes with potassium or a Co(i) complex was achieved to provide the first structurally well-defined aromatic 1,5-diazacyclooctatetraenyl dianion or a novel dinuclear Co(ii) complex bridged by a bipyrrolinyl dianion, respectively. Read More

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http://dx.doi.org/10.1039/c9cc00075eDOI Listing
February 2019

Designing redder and brighter fluorophores by synergistic tuning of ground and excited states.

Chem Commun (Camb) 2019 Feb 11. Epub 2019 Feb 11.

Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, OR 97331, USA.

We strategically modified the GFP core via chemical synthesis to make redder and brighter biomimetic fluorophores. Based on quantum calculations, solvatochromism analysis, and femtosecond Raman, we unveiled the additive effect of tuning the electronic ground and excited states, respectively, to achieve a dramatic emission redshift with a "double-donor-one-acceptor" structure. Read More

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http://xlink.rsc.org/?DOI=C8CC10007A
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http://dx.doi.org/10.1039/c8cc10007aDOI Listing
February 2019
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Imbalances in cellular immunological parameters in blood predetermine tumor onset in a natural mouse model of breast cancer.

Cancer Immunol Immunother 2019 Feb 11. Epub 2019 Feb 11.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, GSP-7, ul. Miklukho-Maklaya, 16/10, Moscow, 117997, Russia.

The development of new approaches to breast cancer (BC) early diagnosis is an important objective of modern oncology. Although the role of the immune system in cancer initiation process was experimentally well established, the prognostic value of cellular blood immunological parameters (CBIPs) for BC onset prediction was not demonstrated either in clinics or in mouse models. In this study, we focused on revealing informative CBIPs for mammary cancer (MC) onset prediction in the BLRB/BYRB mouse model with a high incidence of natural MC development. Read More

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http://dx.doi.org/10.1007/s00262-019-02312-0DOI Listing
February 2019

The management of diabetes mellitus-imperative role of natural products against dipeptidyl peptidase-4, α-glucosidase and sodium-dependent glucose co-transporter 2 (SGLT2).

Bioorg Chem 2019 Feb 4;86:305-315. Epub 2019 Feb 4.

Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy. Electronic address:

Diabetes mellitus is a chronic metabolic disorder which is rapidly spreading worldwide. It is characterized by persistent elevated blood glucose level above normal values (hyperglycemia) due to defect in either insulin secretion or in insulin action or both of them. Currently approved oral synthetic antidiabetic drugs such as biguanides, thiazolidinediones, sulfonylureas, and meglitinides have shown undesirable side effects. Read More

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http://dx.doi.org/10.1016/j.bioorg.2019.02.009DOI Listing
February 2019
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Integrator is a key component of human telomerase RNA biogenesis.

Sci Rep 2019 Feb 8;9(1):1701. Epub 2019 Feb 8.

Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, Moscow, 143026, Russia.

Telomeres are special DNA-protein structures that are located at the ends of linear eukaryotic chromosomes. The telomere length determines the proliferation potential of cells. Telomerase is a key component of the telomere length maintenance system. Read More

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http://dx.doi.org/10.1038/s41598-018-38297-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368637PMC
February 2019

The impact of long-term organic farming on soil-derived greenhouse gas emissions.

Sci Rep 2019 Feb 8;9(1):1702. Epub 2019 Feb 8.

Department of Soil Sciences, Research Institute of Organic Agriculture (FiBL), Ackerstrasse, CH-5070, Frick, Switzerland.

Agricultural practices contribute considerably to emissions of greenhouse gases. So far, knowledge on the impact of organic compared to non-organic farming on soil-derived nitrous oxide (NO) and methane (CH) emissions is limited. We investigated NO and CH fluxes with manual chambers during 571 days in a grass-clover- silage maize - green manure cropping sequence in the long-term field trial "DOK" in Switzerland. Read More

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http://dx.doi.org/10.1038/s41598-018-38207-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368562PMC
February 2019

The algicidal bacterium shapes a natural plankton community.

Appl Environ Microbiol 2019 Feb 8. Epub 2019 Feb 8.

Institute for Inorganic and Analytical Chemistry, Bioorganic Analytics, Friedrich Schiller University Jena, Lessingstrasse 8, D-07743 Jena, Germany

Plankton communities consist of complex microbial consortia which change over time with. These fluctuations can only be partially explained by limiting resources. Biotic factors such as herbivores and pathogens also contribute to the control of algal blooms. Read More

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http://dx.doi.org/10.1128/AEM.02779-18DOI Listing
February 2019

Anti-Inflammatory Activity of A Polyphenolic Extract from in In Vitro and In Vivo Models of Alzheimer's Disease.

Int J Mol Sci 2019 Feb 7;20(3). Epub 2019 Feb 7.

Department of Biochemical Sciences, Sapienza University of Rome, 00185 Roma, Italy.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and the primary form of dementia in the elderly. One of the main features of AD is the increase in amyloid-beta (Aβ) peptide production and aggregation, leading to oxidative stress, neuroinflammation and neurodegeneration. Polyphenols are well known for their antioxidant, anti-inflammatory and neuroprotective effects and have been proposed as possible therapeutic agents against AD. Read More

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http://dx.doi.org/10.3390/ijms20030708DOI Listing
February 2019

Retroelement-Linked Transcription Factor Binding Patterns Point to Quickly Developing Molecular Pathways in Human Evolution.

Cells 2019 Feb 6;8(2). Epub 2019 Feb 6.

I.M. Sechenov First Moscow State Medical University, Moscow 119991, Russia.

Background: Retroelements (REs) are transposable elements occupying ~40% of the human genome that can regulate genes by providing transcription factor binding sites (TFBS). RE-linked TFBS profile can serve as a marker of gene transcriptional regulation evolution. This approach allows for interrogating the regulatory evolution of organisms with RE-rich genomes. Read More

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http://dx.doi.org/10.3390/cells8020130DOI Listing
February 2019
2 Reads

Structure Activity Relationship of 4-Amino-2-thiopyrimidine Derivatives as Platelet Aggregation Inhibitors.

Med Chem 2019 Feb 8. Epub 2019 Feb 8.

Unità di Medicina III, Azienda Ospedaliera San Paolo, Dipartimento di Medicina Chirurgia e Odontoiatria, Università di Milano, Via di Rudinì 8, I-20142 Milano. Italy.

Background: Platelet aggregation plays a pathogenic role in the development of arterial thrombi, which are responsible for common diseases caused by thrombotic arterial occlusion, such as myocardial infarction and stroke. Much efforts is directed toward developing platelet aggregation inhibitors that act through several mechanisms: the main antiplatelet family of COX-inhibitors, phosphodiesterase inhibitors, and thrombin inhibitors. Recently, the important role in the platelet aggregation of adenosine diphosphate (ADP)-activated P2Y12 and P2Y1 receptors, G-protein coupled receptors of the P2 purinergic family, has emerged, and their inhibitors are explored as potential therapeutic antithrombotics. Read More

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http://dx.doi.org/10.2174/1573406415666190208124534DOI Listing
February 2019

Large-scale meta-analysis of mutations identified in panels of breast/ovarian cancer-related genes - Providing evidence of cancer predisposition genes.

Gynecol Oncol 2019 Feb 4. Epub 2019 Feb 4.

Department of Molecular Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland. Electronic address:

Objective: Germline mutations occurring in the highly penetrant genes BRCA1 and BRCA2 are responsible for only certain cases of familial breast cancer (BC) and ovarian cancer (OC). Thus, the use of NGS multi-gene panel (MGP) testing has recently become very popular.

Methods: To estimate a reliable BC and OC risk associated with pathogenic variants in the selected candidate BC/OC predisposition genes, a comprehensive meta-analysis of 48 MGP-based studies analyzing BC/OC patients was conducted. Read More

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http://dx.doi.org/10.1016/j.ygyno.2019.01.027DOI Listing
February 2019

Mycobacterium tuberculosis metC (Rv3340) derived hydrogen sulfide conferring bacteria stress survival.

J Drug Target 2019 Feb 7:1-35. Epub 2019 Feb 7.

a Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Ministry of Education, School of Life Sciences, Southwest University , Chongqing 400715 , China.

Tuberculosis, especially multidrug resistant cases, remains an enormous public health threat. Mycobacterium tuberculosis metC (Rv3340) an enzyme involved in methionine biosynthesis was identified and characterized for antimicrobial susceptibility. We reported that the overexpression of Rv3340 in Mycobacterium smegmatis (Ms_Rv3340) produces hydrogen sulfide (HS) for its energy in harsh conditions. Read More

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http://dx.doi.org/10.1080/1061186X.2019.1579820DOI Listing
February 2019

aza-Wittig Reaction with Nitriles: How Carbonyl Function Switches from Reacting to Activating.

Org Lett 2019 Feb 7;21(4):1087-1092. Epub 2019 Feb 7.

Department of Chemistry , Lomonosov Moscow State University , Leninskie gory 1-3 , Moscow 119991 , Russia.

Transformations of α-EWG-substituted (electron-withdrawing group, EWG) γ-azidobutyronitriles proceeding via unusual aza-Wittig reactions between the phosphazene and nitrile functions and affording pyrrole-derived iminophosphazenes were developed. α-EWGs were found to control chemoselectivity and, depending on their nature, act as CN group activators (e.g. Read More

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http://dx.doi.org/10.1021/acs.orglett.8b04135DOI Listing
February 2019
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A chemical approach for global protein knockdown from mice to non-human primates.

Cell Discov 2019 5;5:10. Epub 2019 Feb 5.

1Ministry of Education (MOE) Key Laboratory of Protein Sciences, School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084 China.

Although conventional genetic modification approaches for protein knockdown work very successfully due to the increasing use of CRISPR/Cas9, effective techniques for achieving protein depletion in adult animals, especially in large animals such as non-human primates, are lacking. Here, we report a chemical approach based on PROTACs technology that efficiently and quickly knocks down FKBP12 (12-kDa FK506-binding) protein globally in vivo. Both intraperitoneal and oral administration led to rapid, robust, and reversible FKBP12 degradation in mice. Read More

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http://dx.doi.org/10.1038/s41421-018-0079-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361926PMC
February 2019

Editorial: Purinergic Pharmacology.

Front Pharmacol 2019 23;10:21. Epub 2019 Jan 23.

Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.

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http://dx.doi.org/10.3389/fphar.2019.00021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351471PMC
January 2019

Pathway Based Analysis of Mutation Data Is Efficient for Scoring Target Cancer Drugs.

Front Pharmacol 2019 23;10. Epub 2019 Jan 23.

Oncobox Ltd., Moscow, Russia.

Despite the significant achievements in chemotherapy, cancer remains one of the leading causes of death. Target therapy revolutionized this field, but efficiencies of target drugs show dramatic variation among individual patients. Personalization of target therapies remains, therefore, a challenge in oncology. Read More

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https://www.frontiersin.org/article/10.3389/fphar.2019.00001
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http://dx.doi.org/10.3389/fphar.2019.00001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351482PMC
January 2019
4 Reads

Shambhala: a platform-agnostic data harmonizer for gene expression data.

BMC Bioinformatics 2019 Feb 6;20(1):66. Epub 2019 Feb 6.

I.M. Sechenov First Moscow State Medical University, Sechenov University, Moscow, 119991, Russia.

Background: Harmonization techniques make different gene expression profiles and their sets compatible and ready for comparisons. Here we present a new bioinformatic tool termed Shambhala for harmonization of multiple human gene expression datasets obtained using different experimental methods and platforms of microarray hybridization and RNA sequencing.

Results: Unlike previously published methods enabling good quality data harmonization for only two datasets, Shambhala allows conversion of multiple datasets into the universal form suitable for further comparisons. Read More

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http://dx.doi.org/10.1186/s12859-019-2641-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366102PMC
February 2019

Transcription factor CgAzf1 regulates melanin production, conidial development and infection in Colletotrichum gloeosporioides.

Antonie Van Leeuwenhoek 2019 Feb 6. Epub 2019 Feb 6.

Key Laboratory of Green Prevention and Control of Tropical Plant Diseases and Pests (Hainan University), Ministry of Education, Haikou, 570228, China.

Rubber anthracnose caused by Colletotrichum gloeosporioides leads to huge economic loss in the natural rubber industry every year. Conidia of C. gloeosporioides are a major infection source but little is known about molecular mechanisms underlying conidial development and infection. Read More

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http://dx.doi.org/10.1007/s10482-019-01243-1DOI Listing
February 2019
1 Read

Bisulfite-free and base-resolution analysis of 5-methylcytidine and 5-hydroxymethylcytidine in RNA with peroxotungstate.

Chem Commun (Camb) 2019 Feb 6. Epub 2019 Feb 6.

Ludwig Institute for Cancer Research and Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, OX3 7FZ, UK.

5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), two of the best-studied DNA modifications, play crucial roles in normal development and disease in mammals. Although 5-methylcytidine (m5C) and 5-hydroxymethylcytidine (hm5C) have also been identified in RNA, their distribution and biological function in RNA remain largely unexplored, due to the lack of suitable sequencing methods. Here, we report a base-resolution sequencing method for hm5C in RNA. Read More

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http://dx.doi.org/10.1039/c9cc00274jDOI Listing
February 2019
1 Read

Variation in Ceratonia siliqua pod metabolome in context of its different geographical origin, ripening stage and roasting process.

Food Chem 2019 Jun 14;283:675-687. Epub 2019 Jan 14.

Leibniz Institute of Plant Biochemistry, Dept. Bioorganic Chemistry, Weinberg 3, D-06120 Halle (Saale), Germany.

Carob is a legume tree of a considerable commercial importance for the flavor and sweet industry. In this context, it is cultivated mostly for its pods, which are known for their nutritive value and multiple health benefits. However, metabolite patterns, underlying these properties are still mostly uncharacterized. Read More

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http://dx.doi.org/10.1016/j.foodchem.2018.12.118DOI Listing

A Short Chemically Modified dsRNA-Binding PNA (dbPNA) Inhibits Influenza Viral Replication by Targeting Viral RNA Panhandle Structure.

Bioconjug Chem 2019 Feb 15. Epub 2019 Feb 15.

Institute of Bioorganic Chemistry, Polish Academy of Sciences , Noskowskiego 12/14 , 61-704 Poznan , Poland.

RNAs play critical roles in diverse catalytic and regulatory biological processes and are emerging as important disease biomarkers and therapeutic targets. Thus, developing chemical compounds for targeting any desired RNA structures has great potential in biomedical applications. The viral and cellular RNA sequence and structure databases lay the groundwork for developing RNA-binding chemical ligands through the recognition of both RNA sequence and RNA structure. Read More

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http://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00039
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00039DOI Listing
February 2019
1 Read

CdsA is involved in biosynthesis of glycolipid MPIase essential for membrane protein integration in vivo.

Sci Rep 2019 Feb 4;9(1):1372. Epub 2019 Feb 4.

The United Graduate School of Agricultural Sciences, Iwate University, Morioka, Iwate, 020-8550, Japan.

MPIase is a glycolipid that is involved in membrane protein integration. Despite evaluation of its functions in vitro, the lack of information on MPIase biosynthesis hampered verification of its involvement in vivo. In this study, we found that depletion of CdsA, a CDP-diacylglycerol synthase, caused not only a defect in phospholipid biosynthesis but also MPIase depletion with accumulation of the precursors of both membrane protein M13 coat protein and secretory protein OmpA. Read More

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http://dx.doi.org/10.1038/s41598-018-37809-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362211PMC
February 2019
5.078 Impact Factor

Structural insights into FTO's catalytic mechanism for the demethylation of multiple RNA substrates.

Proc Natl Acad Sci U S A 2019 Feb 4. Epub 2019 Feb 4.

Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China;

FTO demethylates internal -methyladenosine (mA) and ,2'--dimethyladenosine (mA; at the cap +1 position) in mRNA, mA and mA in snRNA, and -methyladenosine (mA) in tRNA in vivo, and in vitro evidence supports that it can also demethylate -methyldeoxyadenosine (6mA), 3-methylthymine (3mT), and 3-methyluracil (mU). However, it remains unclear how FTO variously recognizes and catalyzes these diverse substrates. Here we demonstrate-in vitro and in vivo-that FTO has extensive demethylation enzymatic activity on both internal mA and cap mA Considering that 6mA, mA, and mA all share the same nucleobase, we present a crystal structure of human FTO bound to 6mA-modified ssDNA, revealing the molecular basis of the catalytic demethylation of FTO toward multiple RNA substrates. Read More

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http://dx.doi.org/10.1073/pnas.1820574116DOI Listing
February 2019
1 Read
9.809 Impact Factor

New Source of 3D Chitin Scaffolds: The Red Sea Demosponge (Pseudoceratinidae, Verongiida).

Mar Drugs 2019 Feb 1;17(2). Epub 2019 Feb 1.

Institute of Electronics and Sensor Materials, Technische Universität Bergakademie-Freiberg, Freiberg 09599, Germany.

The bioactive bromotyrosine-derived alkaloids and unique morphologically-defined fibrous skeleton of chitin origin have been found recently in marine demosponges of the order Verongiida. The sophisticated three-dimensional (3D) structure of skeletal chitinous scaffolds supported their use in biomedicine, tissue engineering as well as in diverse modern technologies. The goal of this study was the screening of new species of the order Verongiida to find another renewable source of naturally prefabricated 3D chitinous scaffolds. Read More

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http://dx.doi.org/10.3390/md17020092DOI Listing
February 2019
2 Reads

Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH₂ Core and Evaluation of Their Anticancer Activity.

Pharmaceutics 2019 Feb 1;11(2). Epub 2019 Feb 1.

Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany.

Herein, a new Ugi multicomponent reaction strategy is described to enhance activity and solubility of the chemotherapeutic drug chlorambucil through its conjugation to poly(amidoamine) (PAMAM-NH₂) dendrimers with the simultaneous introduction of lipidic (-Pr) and cationic (⁻NH₂) or anionic (⁻COOH) groups. Standard viability assays were used to evaluate the anticancer potential of the water-soluble dendrimers against PC-3 prostate and HT-29 colon cancer cell lines, as well as non-cancerous mouse NIH3T3 fibroblasts. It could be demonstrated that the anticancer activity against PC-3 cells was considerably improved when both chlorambucil and ⁻NH₂ (cationic) groups were present on the dendrimer surface (). Read More

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http://dx.doi.org/10.3390/pharmaceutics11020059DOI Listing
February 2019

Site-Selective and Stereoselective C-H Functionalization of N-Cyclopropylamides via a Directed Remote Metalation Strategy.

Org Lett 2019 Feb 4;21(4):969-973. Epub 2019 Feb 4.

Department of Chemistry and Biotechnology, School of Science , Tallinn University of Technology , Tallinn 12618 , Estonia.

A new methodology for site-selective and stereoselective C-H functionalization of aminocyclopropanes via directed remote lithiation has been developed. Treatment of N-directing group (DG = pivaloyl, tetramethylsuccinimidoyl) arylcyclopropanes with t-BuLi results in a clean β-lithiation and, following quench with electrophiles, leads to a range of cyclopropane derivatives. Sequential double lithiation-methylation to give a dimethylated cyclopropane has been achieved. Read More

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http://dx.doi.org/10.1021/acs.orglett.8b03955DOI Listing
February 2019

Stereoselective synthesis of a phosphonate pThr mimetic via palladium-catalyzed γ-C(sp)-H activation for peptide preparation.

Org Biomol Chem 2019 Feb 4. Epub 2019 Feb 4.

Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.

We report a facile synthetic strategy toward CH2-substituted phosphothreonine mimetics. Herein, inexpensive valine with a directing group was converted into homothreonine via palladium-catalyzed γ-methyl C(sp3)-H bond activation, followed by construction of a phosphorus-carbon bond via the well-developed Appel reaction and Michaelis-Becker reaction with a total yield of 30%. Furthermore, the derived mimetic was applied for solid-phase synthesis of two phosphopeptide inhibitors. Read More

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http://dx.doi.org/10.1039/c8ob02999gDOI Listing
February 2019
3.562 Impact Factor

Successes, failures, and future prospects of prodrugs and their clinical impact.

Expert Opin Drug Discov 2019 Feb 4:1-22. Epub 2019 Feb 4.

a Department of Bioorganic & Pharmaceutical Chemistry, Faculty of Pharmacy , Al-Quds University , Jerusalem , Palestine.

Introduction: Ample efforts have been carried out to improve the efficacy of a variety of drugs. The prodrugs approach was found to be a safe haven for providing medications with improved pharmacokinetic and pharmacodynamic properties. Areas covered: Herein, several selected successful prodrugs are reported and categorized. Read More

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http://dx.doi.org/10.1080/17460441.2019.1567487DOI Listing
February 2019
3.467 Impact Factor

Synthesis and Evaluation of Imidazo[1,2-a]pyridine Analogues of the ZSTK474 Class of Phosphatidylinositol 3-Kinase Inhibitors.

Chem Asian J 2019 Feb 3. Epub 2019 Feb 3.

Assoc. Prof. G.W. Rewcastle, Dr S.A. Gamage, Dr J.A. Spicer, Dr K.Y. Tsang, Dr P.D. O'Connor, Dr J.U. Flanagan, Prof. P.R Shepherd, Prof. W.A. Denny, Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Aucklan, NEW ZEALAND.

Using a scaffold-hopping approach, imidazo[1,2-a]pyridine analogues of the ZSTK474 (benzimidazole) class of phosphatidylinositol 3-kinase (PI3K) inhibitors have been synthesized for biological evaluation. Compounds were prepared using a heteroaryl Heck reaction procedure, involving the palladium-catalysed coupling of 2-(difluoro-methyl)imidazo[1,2-a]pyridines with chloro, iodo or trifluoromethane-sulfonyl-oxy (trifloxy) substituted 1,3,5-triazines or pyrimidines, with the iodo intermediates being preferred in terms of higher yields and milder reaction conditions. The new compounds maintain the PI3K isoform selectivity of their benzimidazole analogues, but in general show less potency. Read More

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http://dx.doi.org/10.1002/asia.201801762DOI Listing
February 2019

Mouse Model for Assessing the Subchronic Toxicity of Organophosphate Pesticides.

Acta Naturae 2018 Oct-Dec;10(4):125-128

Institute of Bioorganic Chemistry, Academicians M.M. Shemyakin and Yu.A. Ovchinnikova RAS, Miklukho-Maklaya Str., 16/10, Moscow, 117997, Russia.

The development of antidotes to organophosphate poisons is an important aspect of modern pharmacology. Recombinant acetylcholinesterase and butyrylcholinesterase are effective DNA-encoded acceptors of organophosphate poisons and, in particular, pesticides. Here, we present the results of a study on the effectiveness of recombinant butyrylcholinesterase (BChE) in modeling organophosphate poisoning caused by oral administration of paraoxon at a dose of 2 mg / kg. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351027PMC
February 2019
1 Read

The Preferable Binding Pose of Canonical Butyrylcholinesterase Substrates Is Unproductive for Echothiophate.

Acta Naturae 2018 Oct-Dec;10(4):121-124

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya Str., 16/10, Moscow, 117997, Russia.

In this paper, we, for the first time, describe the interaction between the butyrylcholinesterase enzyme and echothiophate, a popular model compound and an analogue of the chemical warfare agents VX and VR, at the atomistic level. Competition between the two echothiophate conformations in the active site was found using molecular modeling techniques. The first one is close to the mode of binding of the substrates of choline series (butyrylcholine and butyrylthiocholine) and is inhibitory, since it is unable to react with the enzyme. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351040PMC
February 2019

Identification of Novel Interaction Partners of AIF Protein on the Outer Mitochondrial Membrane.

Acta Naturae 2018 Oct-Dec;10(4):100-109

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, Moscow, 117997, Russia.

In response to the wide variety of external and internal signals, mammalian cells undergo apoptosis, programmed cell death. Dysregulation of apoptosis is involved in multiple human diseases, including cancer, autoimmunity, and ischemic injuries. Two types of apoptosis have been described: the caspase-dependent one, leading to digestion of cellular proteins, and caspase-independent apoptosis, resulting in DNA fragmentation. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351035PMC
February 2019
1 Read

The Mechanism of Fluorescence Quenching of Protein Photosensitizers Based on miniSOG During Internalization of the HER2 Receptor.

Acta Naturae 2018 Oct-Dec;10(4):87-94

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997 , Russia.

The protein photosensitizer miniSOG is a promising agent for photodynamic therapy. The genetically encoded phototoxins 4D5scFv-miniSOG and DARPin-miniSOG specifically bind to the HER2 receptor overexpressed on the surface of cancer cells and promote receptor-mediated internalization of HER2. We show that ingestion of proteins in a complex with the receptor reduces the fluorescent signal of the phototoxic module in endosomes. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351032PMC
February 2019

MoS-quantum dot triggered reactive oxygen species generation and depletion: responsible for enhanced chemiluminescence.

Chem Sci 2019 Jan 15;10(2):497-500. Epub 2018 Oct 15.

Beijing Key Laboratory of Microanalytical Methods and Instrumentation , MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology , Department of Chemistry , Tsinghua University , Beijing , 100084 , China . Email:

Reactive oxygen species (ROS) generation is of intense interest because of its crucial role in many fields. Here we demonstrate that MoS-QDs exhibit a promising capability for the generation of reactive oxygen species, which leads to enhanced chemiluminescence. We discovered that the unique performance is due to hydroxyl radical activation increasing the active catalytic sites on molybdenum sulphide quantum dots (MoS-QDs). Read More

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http://dx.doi.org/10.1039/c8sc03511cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334262PMC
January 2019