6,098 results match your criteria ChemBioChem [Journal]


Predicting the substrate scope of the flavin-dependent halogenase BrvH.

Chembiochem 2020 Jul 9. Epub 2020 Jul 9.

University of Bielefeld, Department of Organic Chemistry, PO Box 100131, 33501, Bielefeld, GERMANY.

The recently described flavin-dependent halogenase BrvH is able to catalyze both bromination and chlorination of indole, but shows significantly higher bromination activity. BrvH was annotated as a tryptophan halogenase, but does not accept tryptophan as a substrate. Its native substrate remains unknown. Read More

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http://dx.doi.org/10.1002/cbic.202000444DOI Listing

Cancer Cell Metabolites: Updates on Current Tracing Methods.

Chembiochem 2020 Jul 8. Epub 2020 Jul 8.

Universiti Putra Malaysia, Human Anatomy, MALAYSIA.

Cancer is the second leading cause of death and, 1 in 6 deaths globally is due to cancer. Cancer metabolism is a complex and one of the most actively researched area in cancer biology. Metabolic reprogramming in cancer cells entails activities which involves several enzymes and metabolites to convert nutrient into building blocks that alter energy metabolism to fuel rapid cell division. Read More

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http://dx.doi.org/10.1002/cbic.202000290DOI Listing

Catalytic promiscuity of cGAS: A facile enzymatic synthesis of 2'-3' linked cyclic dinucleotides.

Chembiochem 2020 Jul 7. Epub 2020 Jul 7.

TU Dortmund, Department of Biochemical and Chemical Engineering, Emil-Figge-Str. 66, 44221, Dortmund, GERMANY.

Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that catalyzes the synthesis of cyclic GMP-AMP dinucleotide 2'3'-cGAMP. 2'3'-cGAMP functions as inducer for the production of type I interferons. Derivatives of this important second messenger are highly valuable for pharmaceutical applications. Read More

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http://dx.doi.org/10.1002/cbic.202000433DOI Listing

Perfluorocarbons in Chemical Biology.

Chembiochem 2020 Jul 6. Epub 2020 Jul 6.

UCLA, Chemistry and Biochemistry, 607 Charles E Young Dr, MSB 4505A, 90095, Los Angeles, UNITED STATES.

Perfluorocarbons, saturated carbon chains where all the hydrogen atoms are replaced with fluorine, form a separate phase from both organic and aqueous solutions. Though perfluorinated compounds are not found in living systems, they can be used to modify biomolecules to confer orthogonal behavior within natural systems, such as improved stability, engineered assembly, and cell-permeability. Perfluorinated groups also provide handles for purification, mass-spectrometry, and 19 F NMR studies in complex environments. Read More

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http://dx.doi.org/10.1002/cbic.202000297DOI Listing

The Ubiquitin Enigma: Progress in the Detection and Chemical Synthesis of Branched Ubiquitin Chains.

Chembiochem 2020 Jul 4. Epub 2020 Jul 4.

University of Science and Technology of China, Department of Chemistry, CHINA.

Ubiquitin chains with distinct topologies play essential roles in eukaryotic cells. Recently, it was discovered that multiple ubiquitin units can be ligated to more than one lysine residue in the same ubiquitin to form diverse branched ubiquitin chains. Although there is increasing evidence implicating these branched chains in a plethora of biological functions, few mechanistic details have been elucidated. Read More

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http://dx.doi.org/10.1002/cbic.202000295DOI Listing

Morphological profiling enables the identification of common mode of action for small molecules with different targets.

Chembiochem 2020 Jul 3. Epub 2020 Jul 3.

Max-Planck-Institut für molekulare Physiologie, Chemische Biologie, GERMANY.

Unbiased morphological profiling of bioactivity, e. g. in the cell painting assay (CPA), enables identification of small-molecule mode of action based on similarity to bioactivity of reference compounds and irrespective of biological target and chemical similarity. Read More

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http://dx.doi.org/10.1002/cbic.202000381DOI Listing

Reexamination of the Ergothioneine Biosynthetic Methyltransferase EgtD from Mycobacterium tuberculosis as a Protein Kinase Substrate.

Chembiochem 2020 Jul 2. Epub 2020 Jul 2.

Department for Chemistry, University of Basel, Mattenstrasse 24a, 4002, Basel, Switzerland.

Ergothioneine has emerged as a crucial cytoprotectant in the pathogenic lifestyle of Mycobacterium tuberculosis. Production of this antioxidant from primary metabolites may be regulated by phosphorylation of Thr213 in the active site of the methyltransferase EgtD. The structure of mycobacterial EgtD suggests that this post-translational modification would require a large-scale change in conformation to make the active-site residue accessible to a protein kinase. Read More

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http://dx.doi.org/10.1002/cbic.202000232DOI Listing

Human Cellular Retinol Binding Protein II Forms a Domain-Swapped Trimer Representing a Novel Fold and a New Template for Protein Engineering.

Chembiochem 2020 Jun 30. Epub 2020 Jun 30.

Michigan State University, Chem, 578 S Shaw lane, 48824, United States, 48824, East Lansing, UNITED STATES.

Domain-swapping is a mechanism for evolving new protein structure from extant scaffolds, and has been an efficient protein engineering strategy for tailoring functional diversity. However, domain-swapping can only be exploited if it can be controlled, especially in cases where various folds can coexist. Herein, we describe the structure of a domain-swapped trimer of the iLBP family member, hCRBPII, and suggest a mechanism for domain-swapped trimerization. Read More

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http://dx.doi.org/10.1002/cbic.202000405DOI Listing

Genetic code expansion strategies for vaccine development.

Chembiochem 2020 Jun 30. Epub 2020 Jun 30.

Rijksuniversiteit Groningen, Stratingh Institute for Chemistry, Nijenborgh 4, 9747 AG, Groningen, NETHERLANDS.

By providing long-term protection against infectious diseases vaccinations have significantly reduced death and morbidity world-wide. In the 21 st century, (bio)technological advances have paved the way for developing prophylactic vaccines that are safer and more effective as well as enabled the use of vaccines as therapeutics to treat human diseases. Here, we provide a focused review on the utility of genetic code expansion as an emerging tool for the development of vaccines. Read More

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http://dx.doi.org/10.1002/cbic.202000343DOI Listing

The molecular basis for purine binding selectivity in the bacterial ATP synthase ε subunit.

Chembiochem 2020 Jun 30. Epub 2020 Jun 30.

Bioinformatics Institute, Multiscale Modelling and Design Division, Bioinformatics Institute, 30 Biopolis Street, 138671, Singapur, Singapore, SINGAPORE.

The ε subunit of ATP synthases has been proposed to regulate ATP hydrolysis in bacteria. Prevailing evidence supports the notion that when the ATP concentration falls below a certain threshold, the ε subunit changes its conformation from a non-inhibitory down-state to an extended up-state which then inhibits enzymatic ATP hydrolysis by binding to the catalytic domain. It has been demonstrated that the ε subunit from Bacillus PS3 is selective for ATP over other nucleotides, including GTP. Read More

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http://dx.doi.org/10.1002/cbic.202000291DOI Listing

Inducible genetic code expansion in eukaryotes.

Chembiochem 2020 Jun 29. Epub 2020 Jun 29.

EMBL, Structural and Computational Biology Unit, Meyerhofstrasse 1, 69117, Heidelberg, GERMANY.

Genetic code expansion (GCE) is a versatile tool to site-specifically incorporate a noncanonical amino acid (ncAA) into a protein to e.g. perform fluorescent labeling inside living cells. Read More

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http://dx.doi.org/10.1002/cbic.202000338DOI Listing

Structure-based design of fluorogenic substrates selective for human proteasome subunits.

Chembiochem 2020 Jun 29. Epub 2020 Jun 29.

Universiteit Leiden Faculteit der Wiskunde en Natuurwetenschappen, Bioorganic synthesis, Einsteinweg 55, 2333CC, Leiden, NETHERLANDS.

Proteasomes are established therapeutic targets for hematological cancers and promising targets for autoimmune diseases. In the past we designed and synthesized mechanism-based proteasome inhibitors selective for individual catalytic activities of human constitutive proteasomes and immunoproteasomes: β1c, β1i, β2c, β2i, β5c and β5i. We show here that by taking the oligopeptide recognition element and substituting the electrophile for a fluorogenic leaving group fluorogenic substrates are obtained that report on the proteasome catalytic activity also targeted by the parent inhibitor. Read More

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http://dx.doi.org/10.1002/cbic.202000375DOI Listing

Environmental performance of Pseudomonas putida with a uracylated genome.

Chembiochem 2020 Jun 29. Epub 2020 Jun 29.

Consejo Superior de Investigaciones Cientificas, CNB, SPAIN.

A variant of the soil bacterium Pseudomonas putida with a genome containing a ∼ 20% replacement of the whole of thymine (T) by uracil (U) was made by deleting genes ung (uracil DNA glycosylase) and dut ( deoxyuridine 5'-triphosphate nucleotide hydrolase) . Proteomic comparisons revealed of 281 up-regulated and 96 down-regulated proteins in the ∆ ung ∆ dut cells as compared to the wild-type, many of them involved in nucleotide metabolism. Unexpectedly, genome uracylation did not change much the gross environmental endurance profile of P. Read More

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http://dx.doi.org/10.1002/cbic.202000330DOI Listing

Efficient Chemoenzymatic Synthesis of N-Glycans with a β1,4-Galactosylated Bisecting-GlcNAc Motif.

Chembiochem 2020 Jun 28. Epub 2020 Jun 28.

Universität Bayreuth, Bioorganische Chemie, Gebäude NWI, 95440, Bayreuth, GERMANY.

In human serum immunoglobulin G (IgG) a rare modification of biantennary complex N-glycans leads to a  b 1,4-galactosylated bisecting-GlcNAc branch. We found that the bisecting-GlcNAc on a biantennary core-fucosylated N-glycan was enzymatically galactosylated under stringent reaction conditions. Further optimizations led to an efficient enzymatic approach to this particular modification for biantennary substrates. Read More

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http://dx.doi.org/10.1002/cbic.202000268DOI Listing

Complete Photochemical Regulation of 8-17 DNAzyme Activity using Reversible DNA Photo-cross-linking.

Chembiochem 2020 Jun 28. Epub 2020 Jun 28.

Japan Advanced Institute Science and Technology, The School of Materials and Science, asahi-dai 1-1, 923-1292, Nomi-gun Tatunokutimati, JAPAN.

The regulation of DNAzyme activity is an important problem for its in vivo applications. We achieved photochemical regulation of DNAzyme activity using reversible DNA photo-cross-linking of 3-cyanovinylcarbazole ( CNV K). The ODN containing CNV K photo-cross-linked to pyrimidine base in complementary strand with a few seconds of photoirradiation and its photoadduct was photo-split by photoirradiation with another wavelength. Read More

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http://dx.doi.org/10.1002/cbic.202000227DOI Listing

Trimethylation of the R5 silica-precipitating peptide increases silica particle size by redirecting orthosilicate binding.

Chembiochem 2020 Jun 28. Epub 2020 Jun 28.

University of Washington, Chemistry, Box 351700, 98195, Seattle, UNITED STATES.

The unmodified R5 peptide from silaffin in the diatom Cylindrotheca fusiformis rapidly precipitates silica particles from neutral aqueous solutions of orthosilicic acid. A range of post-translational modifications found in R5 contribute toward tailoring silica morphologies in a species-specific manner. We investigated the specific effect of R5 lysine side-chain trimethylation, which adds permanent positive charges, on silica particle formation. Read More

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http://dx.doi.org/10.1002/cbic.202000264DOI Listing

First Workshop on Metals in Medicine (2019): Translational Research in Medicinal Bioinorganic Chemistry.

Chembiochem 2020 Jun 26. Epub 2020 Jun 26.

Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, 75005, Paris, France.

On the 14-15th November 2019, the first workshop on Metals in Medicine took place in Paris at Chimie ParisTech, PSL University. Organised with the aim of having invited speakers share their experience in bringing metal-based drugs to (pre-)clinical trials, this event gathered 135 attendees from six continents to Paris. A special collection on this event has now been published in ChemBioChem, combining more than 20 articles on different topics related to metals in medicine. Read More

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http://dx.doi.org/10.1002/cbic.202000329DOI Listing

A hydroxyquinoline-based unnatural amino acid for the design of novel artificial metalloenzymes.

Chembiochem 2020 Jun 25. Epub 2020 Jun 25.

University of Groningen, Stratingh Institute for Chemistry, Nijenborgh 4, 9747 AG, Groningen, NETHERLANDS.

Here we examine the potential of the non-canonical amino acid (8-hydroxyquinolin-3-yl)alanine (HQAla) for the design of artificial metalloenzymes. HQAla, a versatile chelator of late transition metals, was introduced into the Lactococcal multidrug resistance regulator (LmrR) via stop codon suppression methodology. LmrR_HQAla was shown to efficiently complex with three different metal ions, Cu II- , Zn II and Rh III to form unique artificial metalloenzymes. Read More

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http://dx.doi.org/10.1002/cbic.202000306DOI Listing

Deacylation of calcium-dependent antibiotics from Streptomyces violaceoruber in co-culture with Streptomyces sp. MG7-G1.

Chembiochem 2020 Jun 25. Epub 2020 Jun 25.

University Konstanz, Chemical Ecology/Biological Chemistry, Universitätsstrasse 10, 78457, Konstanz, GERMANY.

When Streptomyces violaceoruber grows together with Streptomyces sp. MG7-G1, it reacts with strongly induced droplet production on its aerial mycelium. Initially the metabolite profile of droplets from S. Read More

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http://dx.doi.org/10.1002/cbic.202000404DOI Listing

Cationic Ru(II) cyclopentadienyl complexes with antifungal activity against several Candida species.

Chembiochem 2020 Jun 23. Epub 2020 Jun 23.

Institut national de la recherche scientifique, Institut Armand-Frappier, 531 boul. des Prairies, H7V 1B7, Laval, CANADA.

Fungal infections, including those caused by antifungal-resistant  Candida , are a very challenging health problem worldwide. Whereas different ruthenium complexes were previously studied for their anti- Candida  potential, Ru-cyclopentadienyl complexes were overlooked. Here, we report an antifungal activity assessment of three Ru-cyclopentadienyl complexes with some insights into their potential mode of action. Read More

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http://dx.doi.org/10.1002/cbic.202000254DOI Listing

Probing the interaction between HIV-1 protease and the homodimeric p66/p66' reverse transcriptase precursor by double electron-electron resonance EPR spectroscopy.

Chembiochem 2020 Jun 18. Epub 2020 Jun 18.

NIDDK, National Institutes of Health, Department of Chemical Physics, bldg 5, rm b1-30i, 5 medical center drive, 20892-0520, Bethesda, UNITED STATES.

Following excision from the Gag-Pol polyprotein, HIV-1 reverse transcriptase is released as an asymmetric homodimer comprising two structurally dissimilar but amino acid sequence identical p66 subunits. Subsequent cleavage of the RNase H domain from only one of the subunits, denoted as p66', results in the formation of the mature p66/p51 enzyme in which catalytic activity resides in the p66 subunit and the p51 subunit (derived from p66') provides a supporting structural scaffold. Here we probe the interaction of the p66/p66' asymmetric reverse transcriptase precursor with HIV-1 protease by pulsed Q-band double electron-electron resonance EPR spectroscopy to measure distances between nitroxide labels introduced at surface engineered cysteine residues. Read More

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http://dx.doi.org/10.1002/cbic.202000263DOI Listing

Multiple chemical features impact biological performance diversity of a highly active natural product-inspired library.

Chembiochem 2020 Jun 17. Epub 2020 Jun 17.

University of Illinois at Chicago, Chemistry, 845 W. Taylor Street, 60607, Chicago, UNITED STATES.

A systematic, diversity-oriented synthesis approach was employed to access a natural product-inspired flavonoid library with diversity of chemical features, including chemical properties, scaffold, stereochemistry, and appendages. Using Cell Painting, the effects of these diversity elements were evaluated and multiple chemical features that predict biological performance diversity were identified. Scaffold identity appears to be the dominant predictor of performance diversity, but stereochemistry and appendages also contribute to a lesser degree. Read More

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http://dx.doi.org/10.1002/cbic.202000356DOI Listing

Near-infrared probe based on novel fluorescence quenching mechanism for detection of cysteine in bioimaging.

Chembiochem 2020 Jun 18. Epub 2020 Jun 18.

Henan University, School of Materials Science and Engineering, CHINA.

The near-infrared (NIR) fluorescent probe is greatly significant for detecting cysteine (Cys) in biological systems. Herein, we reported a highly selective and sensitive NIR turn-on fluorescent probe ( BDP-NIR ) based on BODIPY with large Stokes shift (105 nm) for detecting Cys. The sensing mechanism based on the different thiols-induced S N Ar substitution-rearrangement reaction of the probe with Cys and Hcy/GSH, leading to the corresponding amino- and thiol-BODIPY dyes with distinct photo-physical properties was clarified. Read More

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http://dx.doi.org/10.1002/cbic.202000313DOI Listing

The Rieske Oxygenase SnoT Catalyzes 2''-Hydroxylation of l-Rhodosamine in Nogalamycin Biosynthesis.

Chembiochem 2020 Jun 17. Epub 2020 Jun 17.

University of Turku, Department of Biochemistry and Food Chemistry, Vatselankatu 2, 20014, Turku, FINLAND.

Nogalamycin is an anthracycline anti-cancer agent that intercalates into the DNA double helix. The binding is facilitated by two carbohydrate units l-nogalose and l-nogalamine, which interact with the minor and major grooves of DNA, respectively. However, recent investigations have shown that nogalamycin biosynthesis proceeds through attachment of l-rhodosamine (2¢¢-deoxy-4¢¢-epi-l-nogalamine) to the aglycone. Read More

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http://dx.doi.org/10.1002/cbic.202000229DOI Listing

Convergent evolution of fungal cysteine dioxygenases.

Chembiochem 2020 Jun 16. Epub 2020 Jun 16.

University of Basel, Department of Chemistry, St. Johanns-Ring 19, 4056, Basel, SWITZERLAND.

Cupin-type cysteine dioxygenases (CDO) are non-heme iron enzymes that occur in animals, plants, bacteria and in filamentous fungi. In this report show that agaricomycetes contain an entirely unrelated type of CDOs that emerged by convergent evolution from enzymes involved in the biosynthesis of ergothioneine. The activity of this CDO type is dependent on the ergothioneine precursor N-α-trimethylhistidine. Read More

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http://dx.doi.org/10.1002/cbic.202000317DOI Listing

Fragment-based discovery of non-bisphosphonate binders of Trypanosoma brucei farnesyl pyrophosphate synthase.

Chembiochem 2020 Jun 14. Epub 2020 Jun 14.

Novartis Institutes for BioMedical Research, NIBR/CBT, Lichtstrasse, WSJ-Virchow-16.3.249, Novartis Campus, 4002, Basel, SWITZERLAND.

Trypanosoma brucei (T. brucei) is the causative agent of Human African Trypanosomiasis (HAT). Nitrogen-containing bisphosphonates, a current treatment for bone diseases, have been shown to block the growth of the T. Read More

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http://dx.doi.org/10.1002/cbic.202000246DOI Listing

Probing the compatibility of an enzyme-linked immunosorbent assay toward the reprogramming of nonribosomal peptide synthetase adenylation domains.

Chembiochem 2020 Jun 12. Epub 2020 Jun 12.

Kindai University, Faculty of Pharmacy, JAPAN.

An important challenge in natural product biosynthesis is the biosynthetic design and production of artificial peptides. One of the most promising strategies is reprogramming adenylation (A) domains to expand the substrate repertoire of nonribosomal peptide synthetase (NRPS) enzymes. Therefore, the precise detection of subtle structural changes in the substrate binding pockets of A-domains may accelerate their reprogramming. Read More

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http://dx.doi.org/10.1002/cbic.202000206DOI Listing

Expanding the genetic code for neuronal studies.

Chembiochem 2020 Jun 12. Epub 2020 Jun 12.

Eberhard Karls Universitat Tubingen, Werner Reichardt Centre for Integrative Neuroscience, Otfried-Müller-Straße 25, 72076, Tübingen, GERMANY.

Genetic code expansion is one of the most powerful technologies in protein engineering . In addition to the 20 canonical amino acids, the expanded genetic code is supplemented by unnatural amino acids. Unnatural amino acids carry artificial side chains that can be introduced into target proteins in vitro and in vivo. Read More

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http://dx.doi.org/10.1002/cbic.202000300DOI Listing

Design and Evaluation of Artificial Hybrid Photoredox Biocatalysts.

Chembiochem 2020 Jun 11. Epub 2020 Jun 11.

University of North Carolina at Chapel Hill, Chemistry, 125 South Rd., CB 3290, North Carolin, Chapel Hill, UNITED STATES.

A pair of 9-mesityl-10-phenyl acridinium (Mes-Acr + ) photoredox catalysts were synthesized with an iodoacetamide handle for cysteine bioconjugation. Covalently tethering of the synthetic Mes-Acr + cofactors with a small panel of thermostable protein scaffolds resulted in twelve newly reported artificial enzymes. The unique chemical and structural environment of the protein hosts had a measurable effect on the photophysical properties and photocatalytic activity of the cofactors. Read More

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http://dx.doi.org/10.1002/cbic.202000362DOI Listing

Photochemical RNA editing of C to U using ultrafast reversible RNA photo-cross-linking in DNA/RNA duplexes.

Chembiochem 2020 Jun 9. Epub 2020 Jun 9.

Japan Advanced Institute Science and Technology, The School of Materials and Science, asahi-dai 1-1, 923-1292, Nomi-gun Tatunokutimati, JAPAN.

RNA editing is used to edit nucleobases in RNA strands; it is more feasible for use in medical applications than DNA editing. We previously reported the photochemical conversion of cytosine to uracil, which required photo-cross-linking, deamination, and photo-splitting. Here, we evaluated the influence of bases surrounding target cytosine on the conversion of cytosine to uracil in the RNA strand. Read More

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http://dx.doi.org/10.1002/cbic.202000269DOI Listing

An Effective Method for Quantifying RNA Expression of IbsC-SibC, a Type I Toxin-Antitoxin System in Escherichia coli.

Chembiochem 2020 Jun 9. Epub 2020 Jun 9.

McMaster University, Biochemistry and Biomedical Sciences, 1280 Main Street West, L8S4K1, Hamilton, CANADA.

Toxin and antitoxin (TA) systems are small genetic modules consisting of a toxin protein and an RNA or protein antitoxin. It is difficult to study their functions in a large part due to the lack of effective methods to study toxin RNAs that usually exist at exceptionally low levels. Herein we describe a sensitive reverse transcription quantitative PCR (RT-qPCR) method that is able to quantitate such RNA species. Read More

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http://dx.doi.org/10.1002/cbic.202000280DOI Listing

Cofactors as molecular fossils to trace the origin and evolution of proteins.

Chembiochem 2020 Jun 9. Epub 2020 Jun 9.

Huazhong Agricultural University, College of Informatics, Shizishan Street 1#, 430070, Wuhan, CHINA.

Due to their early origin and extreme conservation, cofactors are valuable molecular fossils for tracing the origin and evolution of proteins. First, since the order of protein folds binding with cofactors roughly coincides with protein fold chronology, cofactors are considered to have facilitated the origin of primitive proteins by selecting them from a pool of random amino acid sequences. Second, in the subsequent evolution of proteins, cofactors still played an important role. Read More

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http://dx.doi.org/10.1002/cbic.202000027DOI Listing

Tumor suppressor p53TAD1-60 forms a fuzzy complex with metastasis associated S100A4: structural insights and dynamics by an NMR/MD approach.

Chembiochem 2020 Jun 8. Epub 2020 Jun 8.

ELTE Eötvös Loránd University, Institute of Chemistry, Pázmány Péter sétány 1/A, 1117, Budapest, HUNGARY.

Conformationally flexible protein complexes represent a major challenge for structural and dynamical studies. We present a method based on a hybrid NMR/MD approach to characterize the complex formed between the disordered p53TAD 1-60 and the metastasis associated S100A4. Disorder-to-order transition of both TAD1 and TAD2 subdomains upon interaction is detected. Read More

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http://dx.doi.org/10.1002/cbic.202000348DOI Listing

Exploring the Chemoselectivity towards Cysteine Arylation by Cyclometallated Au Compounds: New Mechanistic Insights.

Chembiochem 2020 Jun 8. Epub 2020 Jun 8.

Department of Chemistry, Technical University of Munich, Lichtenbergstrasse 4, 85747, Garching, Germany.

To gain more insight into the factors controlling efficient cysteine arylation by cyclometallated Au complexes, the reaction between selected gold compounds and different peptides was investigated by high-resolution liquid chromatography electrospray ionization mass spectrometry (HR-LC-ESI-MS). The deduced mechanisms of C-S cross-coupling, also supported by density functional theory (DFT) and quantum mechanics/molecular mechanics (QM/MM) calculations, evidenced the key role of secondary peptidic gold binding sites in favouring the process of reductive elimination. Read More

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http://dx.doi.org/10.1002/cbic.202000262DOI Listing

Protein NMR spectroscopy at 150 kHz magic-angle spinning continues to improve resolution and mass sensitivity.

Chembiochem 2020 Jun 5. Epub 2020 Jun 5.

ETH Zürich, Department of Physical Chemistry, Wolfgang-Pauli-Strasse 10, 8093, Zürich, SWITZERLAND.

Spectral resolution is key to unleash the structural and dynamic information contained in NMR spectra. Fast magic-angle spinning (MAS) has recently revolutionized the spectroscopy of biomolecular solids. We here report a further remarkable resolution improvement in the spectra of four fully protonated proteins and a small drug molecule, by pushing the MAS rotation frequency even higher, to 150 kHz, than the more routinely used 100 kHz. Read More

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http://dx.doi.org/10.1002/cbic.202000341DOI Listing

Fluorophosphonate-based degrader identifies degradable serine hydrolases by quantitative proteomics.

Chembiochem 2020 Jun 5. Epub 2020 Jun 5.

Pfizer Global Research and Development, Chemical Biology, UNITED STATES.

A bstract Novel chemical biology probes linking a serine hydrolase-directed fluorophosphonate warhead and cereblon-binding pomalidomide were assessed for degradation of serine hydrolases. A quantitative proteomics approach to detect degraded proteins revealed that despite engagement of ~40 serine hydrolases, degradation was achieved for only a single serine hydrolase, lysophospholipase II (LYPLA2). Read More

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http://dx.doi.org/10.1002/cbic.202000253DOI Listing

Multivalent Antibody-Recruiting Macromolecules: Linking Increased Binding Affinity with Enhanced Innate Immune Killing.

Chembiochem 2020 Jun 4. Epub 2020 Jun 4.

Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.

Antibody-recruiting molecules (ARMs) are a novel class of immunotherapeutics. They are capable of introducing antibodies onto disease-relevant targets such as cancer cells, bacterial cells or viruses. This can induce antibody-mediated immune responses such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and antibody-dependent phagocytosis (ADCP), which can kill the pathogen. Read More

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http://dx.doi.org/10.1002/cbic.202000261DOI Listing

Chemical Knockdown of MicroRNA with Small-Molecule Chimeras.

Chembiochem 2020 Jun 4. Epub 2020 Jun 4.

State Key Laboratory of Analytical Chemistry for Life Sciences Jiangsu Key Laboratory of Advanced Organic Materials School of Chemistry and Chemical Engineering Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing, 210023, China.

This concept article introduces the emerging area of small-molecule chimeras (SMCs) for knocking down microRNAs (miRNAs), which are endogenous gene silencers involved in diverse pathological processes. Compared with agents for genetic knockdown, small-molecules hold significant promise in this field due to their ideal pharmacokinetic and pharmacodynamic properties. The SMCs introduced here are hetero-bifunctional molecules comprising small-molecule binders (SMBs) of miRNAs and chemical functionalities that either directly cleave RNAs or recruit ribonucleases to destroy RNAs. Read More

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http://dx.doi.org/10.1002/cbic.202000287DOI Listing
June 2020
3.088 Impact Factor

Insight into Isoprenoid Biosynthesis by Functional Analysis of Isoprenyl Diphosphate Synthases from Mycobacterium vanbaalenii and Mycobacterium tuberculosis.

Chembiochem 2020 Jun 4. Epub 2020 Jun 4.

Niigata University, Department of Applied Biological Chemistry, 8050 Ikarashi-2, 950-2181, Niigata, JAPAN.

Comprehensive functional analyses of E -isoprenyl diphosphate synthases ( E -IDSs) from nonpathogenic Mycobacterium vanbaalenii were performed. Mv0992 and Mv1577 represent a nonaprenyl diphosphate ( E -C 45 ) synthase and a geranylgeranyl diphosphate ( E -C 20 ) synthase, respectively. Although Mv3536 was identified as an E -C 20 synthase using a single enzyme, co-incubation of Mv3536 and Z -IDSs (Mv4662 and Mv3822) strongly suggested its release of an intermediate geranyl diphosphate ( E -C 10 ) during a continuous condensation reaction. Read More

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http://dx.doi.org/10.1002/cbic.202000235DOI Listing

Analysis of modified nucleotide aptamer library generation by thermophilic DNA polymerases.

Chembiochem 2020 Jun 3. Epub 2020 Jun 3.

Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemsitry, Tűzoltó u., 37-47., 1094, Budapest, HUNGARY.

One of the pivotal steps of aptamer selection is the amplification of target specific oligonucleotides by thermophilic DNA polymerases that could be a challenging task if modified nucleotide possessing nucleic acids are to be amplified. Hence, the identification of compatible DNA polymerase and modified nucleotide pairs is inevitable for effective selection of aptamers with non-natural nucleotides. We present an in-depth study of using 5-Indolyl-AA-dUTP (TAdUTP) for generating oligonucleotide libraries for aptamer selection. Read More

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http://dx.doi.org/10.1002/cbic.202000236DOI Listing

First Ring-Expanded Maytansin Lactone Accessed by a New Mutasynthetic Variant.

Chembiochem 2020 Jun 2. Epub 2020 Jun 2.

Institute of Organic Chemistry and, Center of Biomolecular Drug Research (BMWZ), Leibniz University Hannover, Schneiderberg 1B, 30167, Hannover, Germany.

A multiblocked mutant strain (ΔAHBA and Δasm12, asm21) of Actinosynnema pretiosum, the producer of the highly toxic maytansinoid ansamitocin, has been used for the mutasynthetic production of new proansamitocin derivatives. The use of mutant strains that are blocked in the biosynthesis of an early building block as well as in the expression of two tailoring enzymes broadens the scope of chemo-biosynthetic access to new maytansinoids. Remarkably, a ring-expanded macrolactone derived from ansamitocin was created for the first time. Read More

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http://dx.doi.org/10.1002/cbic.202000336DOI Listing

Reducing agent mediated non-enzymatic conversion of  2-oxoglutarate to succinate - implications for oxygenase assays.

Chembiochem 2020 Jun 1. Epub 2020 Jun 1.

University of Oxford, Chemistry, Chemistry Department, University of Oxford, OX13TA, United Kingdom, OX1 3TA, Oxford, UNITED KINGDOM.

L-Ascorbate (L-Asc) is often added to assays with isolated Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases to enhance activity. L-Asc is proposed to be important in catalysis by some 2OG oxygenases in vivo. We report observations on the non-enzymatic conversion of 2OG to succinate which is mediated by hydrogen peroxide (H2O2), generated by reaction of L-Asc and dioxygen. Read More

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http://dx.doi.org/10.1002/cbic.202000185DOI Listing

Increased Lipophilicity of Halogenated Ruthenium(II) Polypyridyl Complexes Leads to Decreased Phototoxicity in vitro when Used as Photosensitizers for Photodynamic Therapy.

Chembiochem 2020 May 30. Epub 2020 May 30.

Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, 75005, Paris, France.

In the fight against cancer, photodynamic therapy is generating great interest thanks to its ability to selectively kill cancer cells without harming healthy tissues. In this field, ruthenium(II) polypyridyl complexes, and more specifically, complexes with dipyrido[3,2-a:2',3'-c]phenazine (dppz) as a ligand are of particular interest due to their DNA-binding and photocleaving properties. However, ruthenium(II) polypyridyl complexes can sometimes suffer from low lipophilicity, which hampers cellular internalisation through passive diffusion. Read More

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http://dx.doi.org/10.1002/cbic.202000289DOI Listing

Targeted Discovery of Tetrapeptides and Cyclic Polyketide-Peptide Hybrids from a Fungal Antagonist of Farming Termites.

Chembiochem 2020 May 29. Epub 2020 May 29.

Chemical Biology of Microbe - Host Interactions, Institution Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Beutenbergstrasse 11a, 07745, Jena, Germany.

Herein, we report the targeted isolation and characterization of four linear nonribosomally synthesized tetrapeptides (pseudoxylaramide A-D) and two cyclic nonribosomal peptide synthetase-polyketide synthase-derived natural products (xylacremolide A and B) from the termite-associated stowaway fungus Pseudoxylaria sp. X187. The fungal strain was prioritized for further metabolic analysis based on its taxonomical position and morphological and bioassay data. Read More

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http://dx.doi.org/10.1002/cbic.202000331DOI Listing

Biocatalytic Alkylation Cascades: Recent Advances and Future Opportunities for Late-Stage Functionalization.

Chembiochem 2020 May 27. Epub 2020 May 27.

Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, United Kingdom.

This Concept article describes the latest developments in the emerging area of late-stage biocatalytic alkylation. Central to these developments is the ability to efficiently prepare S-adenosyl methionine (SAM) cofactor analogues and couple this with enzymatic alkyl transfer. Recent developments in the enzymatic synthesis of SAM cofactor analogues are summarized first, followed by their application as alkyl transfer agents catalyzed by methyltransferases (MTases). Read More

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http://dx.doi.org/10.1002/cbic.202000187DOI Listing

Dynamic Stabilization of DNA Assembly Using Pyrrole-Imidazole Polyamide.

Chembiochem 2020 May 26. Epub 2020 May 26.

National University of Singapore, Chemical and Biomolecular Engineering, Block E5 #02-09, 4 Engineering Drive 4, 117585, Singapore, SINGAPORE.

We used N-methylpyrrole (Py)-N-methylimidazole-(Im) polyamide as an exogenous agent to modulate the formation of DNA assemblies at specific double-stranded sequences. The concept was demonstrated on the hybridization chain reaction which forms linear DNA assembly. Through a series of melting curve analysis, we demonstrated that the binding of Py-Im polyamide positively influenced both the HCR initiation and elongation steps. Read More

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http://dx.doi.org/10.1002/cbic.202000245DOI Listing

Enantioselective Synthesis of Planar Chiral Ferrocifens that Show Chiral Discrimination in Antiproliferative Activity on Breast Cancer Cells.

Chembiochem 2020 May 26. Epub 2020 May 26.

Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin Belfield, Dublin, 4, Ireland.

The design and first enantioselective synthesis of a series of chiral ferrocifens and ferrociphenols was realised by enantioselective palladium-catalysed intramolecular direct C-H bond activation followed by McMurry coupling. Biological evaluation revealed moderate anticancer activities on breast cancer cells and evidence of chiral discrimination between enantiomers. Treatment of the novel ferrocifens with Ag O revealed that these systems are unable to form a neutral quinone methide, yet still demonstrate marked antiproliferative properties against both the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 cell lines. Read More

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http://dx.doi.org/10.1002/cbic.202000311DOI Listing

Nonhydrolyzable Heptose Bis- and Monophosphate Analogues Modulate Pro-inflammatory TIFA-NF-κB Signaling.

Chembiochem 2020 May 26. Epub 2020 May 26.

University of Namur (UNamur), NARILIS, Department of Chemistry, rue de Bruxelles 61, 5000, Namur, Belgium.

d-Glycero-d-manno-heptose-1β,7-bisphosphate (HBP) and d-glycero-d-manno-heptose-1β-phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells through the activation of the TIFA-dependent NF-κB pathway. To better understand structure-based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA-NF-κB signal axis was evaluated in vivo at a low-nanomolar concentration (6 nM) and compared to that of the natural metabolites. Read More

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http://dx.doi.org/10.1002/cbic.202000319DOI Listing

Special Issue on Nitrogenases and Homologous Systems.

Chembiochem 2020 Jun 19;21(12):1668-1670. Epub 2020 May 19.

Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697-3900, USA.

The nitrogenase superfamily comprises homologous enzyme systems that carry out fundamentally important processes, including the reduction of N and CO, and the biosynthesis of bacteriochlorophyll and coenzyme F430. This special issue provides a cross-disciplinary overview of the ongoing research in this highly diverse and unique research area of metalloprotein biochemistry. Read More

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http://dx.doi.org/10.1002/cbic.202000279DOI Listing

Molecular Recognition in C-Type Lectins: The Cases of DC-SIGN, Langerin, MGL, and L-Sectin.

Chembiochem 2020 May 19. Epub 2020 May 19.

CIC bioGUNE, Basque Research Technology Alliance, BRTA, Bizkaia Technology park, Building 800, 48160, Derio, Spain.

Carbohydrates play a pivotal role in intercellular communication processes. In particular, glycan antigens are key for sustaining homeostasis, helping leukocytes to distinguish damaged tissues and invading pathogens from healthy tissues. From a structural perspective, this cross-talk is fairly complex, and multiple membrane proteins guide these recognition processes, including lectins and Toll-like receptors. Read More

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http://dx.doi.org/10.1002/cbic.202000238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276794PMC