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  • Rapid Biophysical Characterization and NMR Spectroscopy Structural Analysis of Small Proteins from Bacteria and Archaea
    ChemBioChem (IF 2.593) Pub Date : 2020-01-21
    Nina Kubatova; Dennis J. Pyper; Hendrik R. A. Jonker; Krishna Saxena; Laura Remmel; Christian Richter; Sabine Brantl; Elena Evguenieva‐Hackenberg; Wolfgang R. Hess; Gabriele Klug; Anita Marchfelder; Jörg Soppa; Wolfgang Streit; Maxim Mayzel; Vladislav Y. Orekhov; Monika Fuxreiter; Ruth A. Schmitz; Harald Schwalbe
    更新日期:2020-01-22
  • Simultaneous Detection of Multiple Pathogenic Targets with Stem‐Tagged Primer Sets
    ChemBioChem (IF 2.593) Pub Date : 2020-01-21
    Yong‐Tae Kim; Junhye Moon; In Seok Hong
    更新日期:2020-01-22
  • 更新日期:2020-01-22
  • 更新日期:2020-01-22
  • Targetable Tetrazine‐Based Dynamic Nuclear Polarization Agents for Biological Systems
    ChemBioChem (IF 2.593) Pub Date : 2020-01-21
    Byung Joon Lim; Bryce E. Ackermann; Galia T. Debelouchina
    更新日期:2020-01-22
  • Live‐Cell Copper‐Induced Fluorescence Quenching of the Flavin‐Binding Fluorescent Protein CreiLOV
    ChemBioChem (IF 2.593) Pub Date : 2020-01-21
    Wenping Zou; Khoa Le; Melissa L. Zastrow
    更新日期:2020-01-22
  • Efficient Generation of Hydrazides in Proteins by RadA Split Intein
    ChemBioChem (IF 2.593) Pub Date : 2020-01-21
    Jun Liu; Oshini Ekanayake; Dominic Santoleri; Kelsi Walker; Sharon Rozovsky
    更新日期:2020-01-22
  • Genetic Encoding of a Bioconjugation Handle for [2+2+2] Cycloaddition Reactions
    ChemBioChem (IF 2.593) Pub Date : 2020-01-21
    Christopher R. Travis; Elizabeth A. King; Gillian H. Gaunt; Douglas D. Young
    更新日期:2020-01-22
  • Terminal Alkynes as Raman Probes of α‐Synuclein in Solution and in Cells
    ChemBioChem (IF 2.593) Pub Date : 2020-01-21
    Jessica D. Flynn; Megan Y. Gimmen; Dexter N. Dean; Shannon M. Lacy; Jennifer C. Lee

    Conformational changes of α‐synuclein (α‐syn) are central to its biological function and Parkinson’s disease pathology. Here, terminal alkynes (homopropargylglycine) were employed as environmentally sensitive Raman probes at residues 1, 5, 116, and 127, to characterize soluble (disordered), micelle‐bound (α‐helical), and fibrillar (β‐sheet) α‐syn. Along with the full‐length protein, a disease‐related C‐terminal truncation (1–115) was also studied. For the first time, β‐sheet α‐syn amyloid structure was detected by the amide‐I band in N27 dopaminergic rat cells, where a reciprocal relationship between levels of fibrils and lipids was seen. Site‐specific spectral features of the terminal alkynes also revealed heterogeneity of the cellular environment. This work shows the versatility of Raman microspectroscopy and the power of unnatural amino acids in providing structural and residue‐level insights in solution and in cells.

    更新日期:2020-01-22
  • Computational design of enantiocomplementary epoxide hydrolases for asymmetric synthesis of aliphatic and aromatic diols
    ChemBioChem (IF 2.593) Pub Date : 2020-01-21
    Hesam Arabnejad; Elvira Bombino; Dana I. Colpa; Peter A. Jekel; Milos Trajkovic; Hein J. Wijma; Dick Janssen

    The use of enzymes in preparative biocatalysis often requires tailoring enzyme selectivity by protein engineering. Here, we explore the use of computational library design and MD simulations to create variants of limonene epoxide hydrolase that produce enantiomeric diols from meso‐epoxides. Three substrates of different sizes were targeted: 2,3‐butene oxide, cyclopentene oxide and cis‐stilbene oxide. Most of the 28 designs tested were active and showed the predicted enantioselectivity. Excellent enantioselectivities were obtained for the bulky substrate cis‐stilbene oxide, and enantio­complementary mutants produced (S,S)‐ and (R,R)‐stilbene diol with >97% enantiomeric excess. An (R,R)‐selective mutant was used to prepare (R,R)‐stilbene diol with high enantiopurity (98% conversion to diol, >99 % e.e.). Some variants displayed higher catalytic rates (kcat) than the original enzyme, but in most cases KM values increased as well. The results demonstrate the feasibility of computational design and screening to engineer enantioselective epoxide hydrolase variants with very limited laboratory screening.

    更新日期:2020-01-22
  • Pyrene‐Based Noncovalent Immobilization of Nitrogenase on Carbon Surfaces
    ChemBioChem (IF 2.593) Pub Date : 2020-01-20
    Janki Patel; Rong Cai; Ross Milton; Hui Chen; Shelley D. Minteer
    更新日期:2020-01-21
  • Calcium Regulates S100A12 Zinc Sequestration by Limiting Structural Variations
    ChemBioChem (IF 2.593) Pub Date : 2020-01-20
    Qian Wang; Aleksey Aleshintsev; Aneesha N. Jose; James M. Aramini; Rupal Gupta
    更新日期:2020-01-21
  • Hybridizing Oligonucleotides with Hydrophobic Peptide Nucleic Acids Assists Their Cellular Uptake through Aggregate Formation
    ChemBioChem (IF 2.593) Pub Date : 2020-01-20
    Sotaro Misu; Ryohsuke Kurihara; Reina Kainuma; Ryugai Sato; Tatsuya Nishihara; Kazuhito Tanabe
    更新日期:2020-01-21
  • Synthesis of Cyclic Sulfite Diesters and their Evaluation as Sulfur Dioxide (SO2) Donors
    ChemBioChem (IF 2.593) Pub Date : 2020-01-20
    Satish R. Malwal; Kundansingh A. Pardeshi; Harinath Chakrapani
    更新日期:2020-01-21
  • Coculturing of Mosquito‐Microbiome Bacteria Promotes Heme Degradation in Elizabethkingia anophelis
    ChemBioChem (IF 2.593) Pub Date : 2020-01-20
    Jack G. Ganley; Hannah K. D'Ambrosio; Meg Shieh; Emily R. Derbyshire
    更新日期:2020-01-21
  • Photo‐crosslinking: An Emerging Chemical Tool for Investigating Molecular Networks in Live Cells
    ChemBioChem (IF 2.593) Pub Date : 2020-01-20
    Pratyush Kumar Mishra; Chang‐Mo Yoo; Eunmi Hong; Hyun Woo Rhee
    更新日期:2020-01-21
  • Regulation of Immune Activation by Optical Control of TLR1/2 Heterodimerization
    ChemBioChem (IF 2.593) Pub Date : 2020-01-20
    Hong‐Guo Hu; Pu‐Guang Chen; Guanyu Wang; Jun‐Jun Wu; Bo‐Dou Zhang; Wen‐Hao Li; Rebecca L. Davis; Yan‐Mei Li
    更新日期:2020-01-21
  • Extending the Salinilactone Family
    ChemBioChem (IF 2.593) Pub Date : 2020-01-20
    Christian Schlawis; Tim Harig; Stephanie Ehlers; Dulce G Guillen-Matus; K. E. Creamer; Paul Jensen; Stefan Schulz

    Five new members of the salinilactone family, salinilactones D‐H, are reported. These bicyclic lactones are produced by Salinispora bacteria and display extended or shortened alkyl side chains compared to the recently reported salinilactones A‐C. They were identified by GC/MS, gas chromatographic retention index and comparison with synthetic samples. We further investigated the occurrence of salinilactones across six newly proposed Salinispora species to gain insight into how compound production varies among taxa. The growth inhibiting effect of this compound family on multiple biological systems including non‐Salinispora actinomycetes were analyzed. Additionally, we found strong evidence for significant cytotoxicity of the title compounds.

    更新日期:2020-01-21
  • Chimeric Interaction of Nitrogenase‐like Reductases with the MoFe Protein of Nitrogenase
    ChemBioChem (IF 2.593) Pub Date : 2020-01-20
    Jan Jasper; José Vazquez Ramos; Christian Trncik; Dieter Jahn; Oliver Einsle; Gunhild Layer; Jürgen Moser

    The engineering of transgenic organisms with the ability to fix nitrogen is an attractive possibility. However, oxygen sensitivity of nitrogenase, mainly conferred by the reductase component (NifH) 2 is an imminent problem. Nitrogenase‐like enzymes involved in coenzyme F 430 and chlorophyll biosynthesis utilize the highly homologous reductases (CfbC) 2 and (ChlL) 2 , respectively. Chimeric protein‐protein interaction of these reductases with the catalytic component of nitrogenase (MoFe protein) did not support nitrogenase activity. Nucleotide‐dependent association and dissociation of these complexes was investigated but (CfbC) 2 and wild type (ChlL) 2 showed no modulation of the binding affinity. By contrast, the interaction between the (ChlL) 2 mutant Y127S and the MoFe protein was markedly increased in the presence of ATP (or ATP analogs) and reduced in the ADP state. Upon formation of the octameric (ChlL) 2 MoFe(ChlL) 2 complex, the ATPase activity of this variant is triggered as seen in the homologous nitrogenase system. Thus, the described reductase(s) might be an attractive tool for further elucidation of the diverse functions of (NifH) 2 and the rational design of a more robust reductase.

    更新日期:2020-01-21
  • Triazolecarbaldehyde Reagents for One‐Step N‐Terminal Protein Modification
    ChemBioChem (IF 2.593) Pub Date : 2020-01-16
    Akira Onoda; Nozomu Inoue; Eigo Sumiyoshi; Takashi Hayashi
    更新日期:2020-01-17
  • Mechanism of diol dehydration by a promiscuous radical‐SAM enzyme homologue of the antiviral enzyme viperin (RSAD2)
    ChemBioChem (IF 2.593) Pub Date : 2020-01-17
    Kourosh Honarmand Ebrahimi; Jack Rowbotham; James McCullagh; William S James

    3´‐deoxy nucleotides are an important class of drugs because they interfere with metabolism of nucleotides and their incorporation into DNA or RNA terminates cell division and viral replication. These compounds have largely been produced via multistep chemical synthesis and an enzyme with the ability to catalyse removal of 3´‐deoxy group from different nucleotides has yet to be described. Here, using a combination of HPLC, high‐resolution mass spectrometry, and NMR spectroscopy we demonstrate that a thermostable fungal radical S‐adenosylmethionine (SAM) enzyme with similarity to the vertebrate antiviral enzyme viperin (RSAD2) can catalyze transformation of CTP, UTP, and 5‐bromo‐UTP to their 3ʹ‐deoxy‐3′,4ʹ‐didehydro analogues. We show that unlike the fungal enzyme human viperin can only catalyse transformation of CTP. Using electron paramagnetic resonance (EPR) spectroscopy and molecular docking and dynamics simulations in combination with mutagenesis studies we provide insight into the origin of the unprecedented substrate promiscuity of the enzyme and the mechanism of dehydration of a nucleotide. Our findings highlight the evolution of substrate specificity in a member of the radical‐SAM enzymes. We predict that our work will help in utilizing a new class of radical‐SAM enzymes for biocatalytic synthesis of 3ʹ‐deoxy nucleotide/nucleoside analogues.

    更新日期:2020-01-17
  • Comparison of the biocatalytic activity of some halotolerant yeasts in freshwater and seawater
    ChemBioChem (IF 2.593) Pub Date : 2020-01-17
    Cecilia Andreu; Marcel·lí del Olmo

    The application of Green Chemistry concepts in catalysis has considerably increased in recent years, and the interest in using sustainable solvents in the chemical industry is growing. One of the recent proposals to fall in line with this is to employ seawater as a solvent in biocatalytic processes. This involves selecting halotolerant strains capable of carrying out chemical conversions in the presence of the salt concentrations found in this solution. Recent studies by our group have revealed the interest in using strains belonging to Debaryomyces and Schwannyomyces for catalytic processes run in this medium. In this work we select several strains based on their halotolerance to widen the scope of this strategy. We consider them for the monoreduction of 1‐phenylpropane‐1,2‐dione, a well‐characterized reaction that produces intermediates of pharmaceutical interest. The results obtained herein indicate that using seawater as a solvent for this reaction is possible, and it even offers advantages for stereoselectivity and biocatalyst reuse with some strains. The data found for S. cerevisiae FY86 and K. marxianus were particularly interesting.

    更新日期:2020-01-17
  • Biosynthesis and Structure Activity Relationship Investigations of the Diazeniumdiolate Antifungal Agent Fragin
    ChemBioChem (IF 2.593) Pub Date : 2020-01-16
    Simon Sieber; Christophe Daeppen; Christian Jenul; Vidya Mannancherril; Leo Eberl; Karl Gademann

    Only a few natural products possessing a diazeniumdiolate have been isolated and usually these compounds display a broad range of biological activities. Only recently the first diazeniumdiolate natural product biosynthetic gene cluster was identified in Burkholderia cenocepacia H111, which produces the fungicide (—)‐fragin and the signal molecule (rac)‐valdiazen. In this study, L‐valine was identified as the initial substrate of (—)‐fragin biosynthesis by feeding experiments using isotopically labeled amino acids. The formation of the diazeniumdiolate was chemically studied by several proposed intermediates. Our results indicate that the functional group is formed during an early stage of the biosynthesis. Furthermore, an oxime compound was identified as a degradation product of (—)‐fragin and was also observed in the crude extract of the wild type strain. Moreover, structure‐activity relationship analysis revealed that each moiety of (—)‐fragin is essential for its biological activity.

    更新日期:2020-01-17
  • Synthetic approaches for accessing pseudaminic acid (Pse) bacterial glycans
    ChemBioChem (IF 2.593) Pub Date : 2020-01-15
    Emily P. K. Flack; Harriet S Chidwick; Matthew Best; Gavin Thomas; Martin Anthony Fascione

    Pseudaminic acid (Pse5Ac7Ac) is a non‐mammalian sugar with structural similarity to the ubiquitous sialic acid sugar Neu5Ac and an important virulence factor for a number of pathogenic bacteria, including emerging multidrug resistant ESKAPE pathogens. Despite their discovery over 30 years ago, relatively little is known about the biological significance of Pse glycans compared to their sialic acid analogues, primarily due to a lack of access to the synthetically challenging Pse architecture. Recently however the Pse backbone has been subjected to increasing synthetic exploration by carbohydrate (bio)chemists, and the total synthesis of complex Pse glycans achieved using inspiration from the biosynthesis and subsequent detailed study of the chemical glycosylation using Pse donors. In this minireview we provide context for these efforts by summarising the recent synthetic approaches pioneered for accessing Pse glycans, which are set to open up this underexplored area of glycoscience to the wider scientific community.

    更新日期:2020-01-15
  • Identification of human IDO1 Enzyme Activity by Genetically Encoded Nitrotyrosine
    ChemBioChem (IF 2.593) Pub Date : 2020-01-15
    Zhaopeng Zheng; Xuzhen Guo; Minling Yu; Xiaoyan Wang; Hongguang Lu; Fahui Li; Jiangyun Wang

    Human indoleamine 2,3‐dioxygenase 1 (IDO1) has become an increasingly valuable target for cancer immunotherapy because it promotes immune escape by tumor cells. To date, the function of posttranslational modifications (PTMs) on IDO1 has not been fully elucidated. Among the many forms of PTMs, it has been identified that three tyrosine sites (Y15, Y345, and Y353) on IDO1 are nitrated and play important roles in c atalytic function. Herein, by genetically encoded 3‐nitro‐L‐tyrosine (NT) into the tyrosine nitration sites of IDO1, we have obtained the homogeneous and native nitrated‐IDO1. We found that nitration of the different tyrosine sites has different effects on IDO1 structure and enzyme activity. Nitration at position Y15 has a negligible effect, but nitration at Y345 or Y353 decreases the enzyme activity, especially Y353. Furthermore, our results demonstrate that the regulation of the catalytic function caused by tyrosine nitration is related to protein structure perturbation and heme‐binding disruption.

    更新日期:2020-01-15
  • Structure validation for G‐rich RNAs in non‐coding regions of the human genome
    ChemBioChem (IF 2.593) Pub Date : 2020-01-14
    Oliver Binas; Irene Bessi; Harald Schwalbe

    We present here the rapid biophysical characterization of six previously reported putative G‐quadruplex forming RNAs from the 5’‐UTR of silvestrol‐sensitive transcripts to investigate their secondary structure. By NMR and CD spectroscopic analysis, we find that only a single sequence, [AGG] 2 [CGG] 2 C, folds into a single well‑defined G‐quadruplex structure. Sequences with longer poly‐G strands form unspecific aggregates, while CGG‐repeat containing sequences exhibit a temperature‐dependent equilibrium between a hairpin and a G‐quadruplex structure. The applied experimental strategy is fast and provide robust readout for G‐quadruplex forming capacities of RNA oligomers.

    更新日期:2020-01-15
  • Versatile 3’ Functionalization of CRISPR Single Guide RNA
    ChemBioChem (IF 2.593) Pub Date : 2020-01-14
    Cody M. Palumbo; Jeton M. Gutierrez-Bujari; Henriette O’Geen; David J. Segal; Peter Beal

    Specific applications of CRISPR/Cas genome editing systems benefit from chemical modifications of the sgRNA. Here we describe a versatile and efficient strategy for functionalization of the 3’ end of a sgRNA. An exemplary collection of six chemically modified sgRNAs was prepared containing crosslinkers, a fluorophore and biotin. Modification of the sgRNA 3’ end was broadly tolerated by S. pyogenes Cas9 in an in vitro DNA cleavage assay. The 3’‐biotinylated sgRNA was used as an affinity reagent to identify IGF2BP1, YB1 and hnRNP K as sgRNA‐binding proteins present in HEK293T cells. Overall, the modification strategy presented here has the potential to expand on current applications of CRISPR/Cas systems.

    更新日期:2020-01-15
  • Chemo‐Enzymatic Preparation of Functional Click Labelled Messenger RNA
    ChemBioChem (IF 2.593) Pub Date : 2020-01-14
    Stefano Croce; Sascha Serdjukow; Thomas Carell; Thomas Frischmuth

    Nowadays synthetic mRNAs are promising candidates for a new class of transformative drugs, which provide genetic information for patients’ cells to develop their own cure. One key advancement to develop so‐called druggable mRNAs was the preparation of chemically modified mRNAs, by replacing standard bases by modified ones, e.g. uridine with pseudouridine capable to ameliorate the immunogenic profile and translation efficiency of the mRNA. Thus the introduction of modified nucleobases was the foundation for clinical usage of such mRNAs. Herein, we describe modular and simple methods to chemo‐enzymatically modify mRNA. Alkyne and or azide‐modified nucleotides are enzymatically incorporated into mRNA and subsequently conjugated to fluorescent dyes using click chemistry. This allows visualization of the labelled mRNA inside of cells. mRNA coding for the enhanced green fluorescent protein (eGFP) was chosen as a model system and the successful expression of eGFP demonstrated that our modified mRNA is accepted by the translation machinery.

    更新日期:2020-01-14
  • pH‐Dependent Protonation of Surface Carboxylates in PsbO Enables Local Buffering and Triggers Structural Changes
    ChemBioChem (IF 2.593) Pub Date : 2020-01-12
    Lisa Maria Gerland; Daniel Friedrich; Linus Hopf; Eavan Donovan; Arndt Wallmann; Natalja Erdmann; Anne Diehl; Martin Bommer; Krzysztof Buzar; Mohamed Ibrahim; Peter Schmieder; Holger Dobbek; Athina Zouni; Ana-Nicoleta Bondar; Holger Dau; Hartmut Oschkinat

    Photosystem II (PSII) catalyzes the splitting of water, releasing protons and dioxygen. Its highly conserved subunit PsbO extends from the oxygen evolving center (OEC) into the thylakoid lumen and stabilizes the catalytic Mn 4 CaO 5 ‐cluster. The high conservation of accessible, negatively charged surface residues in PsbO suggests additional functions, as local pH buffer or by affecting the flow of protons. For this discussion, we provide an experimental basis by determining pK a values of water‐accessible aspartate and glutamate side chain carboxyl groups using NMR. Their distribution is strikingly uneven, with high pK a values around 4.9 clustering on the luminal PsbO side and values below 3.5 on the side facing PSII. pH‐dependent changes of backbone chemical shifts in the area of the lumen‐exposed loops are observed, indicating conformational changes. In conclusion, we present a site‐specific analysis of carboxyl group proton affinites in PsbO, providing a basis to further understand proton transport in photosynthesis.

    更新日期:2020-01-13
  • S‐Adenosyl‐l‐Methionine Salvage Impacts Psilocybin Formation in “Magic” Mushrooms
    ChemBioChem (IF 2.593) Pub Date : 2020-01-10
    Richard Demmler; Janis Fricke; Sebastian Dörner; Markus Gressler; Dirk Hoffmeister
    更新日期:2020-01-10
  • Structural and Biochemical Insight into the Recruitment of Acyl Carrier Protein‐Linked Extender Units in Ansamitocin Biosynthesis
    ChemBioChem (IF 2.593) Pub Date : 2020-01-10
    Fa Zhang; Huining Ji; Imtiaz Ali; Zixin Deng; Linquan Bai; Jianting Zheng
    更新日期:2020-01-10
  • A Trifunctional Linker for Palmitoylation and Peptide and Protein Localization in Biological Membranes
    ChemBioChem (IF 2.593) Pub Date : 2020-01-10
    Łukasz Syga; Reinder H. de Vries; Hugo van Oosterhout; Rianne Bartelds; Arnold J. Boersma; Gerard Roelfes; Bert Poolman
    更新日期:2020-01-10
  • Quantitative MS‐based proteomics comparing the MCF‐7 cellular response to hypoxia and a 2‐oxoglutarate analogue
    ChemBioChem (IF 2.593) Pub Date : 2020-01-10
    Jacob T. Bush; Mun Chiang Chan; Shabaz Mohammed; Christopher Schofield

    The hypoxia‐inducible factors (HIFs) are key transcription factors in determining cellular responses involving alterations in protein levels in response to limiting oxygen availability in animal cells. 2‐Oxoglurate dependent oxygenases play key roles in regulating HIF levels and its transcriptional activity. We describe MS‐based proteomics studies employing a lysine demethylation‐based approach in which we compared the results of treating human breast cancer MCF‐7 cells with hypoxia or a cell‐penetrating derivative (dimethyl N‐oxalylglycine) of the stable 2OG analogue N‐oxalylglycine. The proteomic results are consistent with reported transcriptomic analyses and support the proposed key roles of 2OG dependent HIF prolyl‐ and asparaginyl‐hydroxylases in the hypoxic response. Differences between the data sets for hypoxia and DMOG may reflect context‐dependent effects or HIF‐independent effects of DMOG

    更新日期:2020-01-10
  • A modified Arrhenius approach to thermodynamically study regioselectivity in Cytochrome P450 catalyzed substrate conversion
    ChemBioChem (IF 2.593) Pub Date : 2020-01-09
    Rosa A. Luirink; Marlies C.A. Verkade-Vreeker; Jan N.M. Commandeur; Daan Geerke

    The regio‐ (and stereo‐) selectivity and specific activity of Cytochrome P450s are determined by the accessibility of potential sites‐of‐metabolism (SOMs) of the bound substrate relative to the heme, and the activation barrier of the regioselective oxidation reaction. The accessibility of potential SOMs depends on the relative binding free energy ΔΔ G bind of the catalytically active substrate‐binding poses, and the probability of the substrate to adopt a transition state geometry. An established experimental method to measure activation energies of enzymatic reactions is the analysis of reaction‐rate constants at different temperatures and the construction of Arrhenius plots. This is a challenge for multi‐step P450‐catalyzed processes which involve redox partners. We introduce a modified Arrhenius approach to overcome the limitations in studying P450 selectivity, which can be applied in multi‐product enzyme catalysis. Our approach gives combined information on relative activation energies, ΔΔ G bind values and collision entropies, yielding direct insights into the basis of selectivity in substrate conversion.

    更新日期:2020-01-10
  • Real‐Time BODIPY‐Binding Assay To Screen Inhibitors of the Early Oligomerization Process of Aβ1–42 Peptide
    ChemBioChem (IF 2.593) Pub Date : 2020-01-09
    Nicolo Tonali; Veronica I. Dodero; Julia Kaffy; Loreen Hericks; Sandrine Ongeri; Norbert Sewald
    更新日期:2020-01-09
  • Development of Polyamine‐Substituted Triphenylamine Ligands with High Affinity and Selectivity for G‐Quadruplex DNA
    ChemBioChem (IF 2.593) Pub Date : 2020-01-09
    Isabel Pont; Álvaro Martínez‐Camarena; Cristina Galiana‐Roselló; Roberto Tejero; M. Teresa Albelda; Jorge González‐García; Ramón Vilar; Enrique García‐España
    更新日期:2020-01-09
  • 更新日期:2020-01-09
  • Design and expeditious synthesis of quinoline‐pyrene based ratiometric fluorescent probes for targeting lysosomal pH
    ChemBioChem (IF 2.593) Pub Date : 2020-01-09
    Santosh J. Gharpure; Shobhna Kapoor; Pankaj Hande; Manjari Mishra; Anindya Datta; Fariyad Ali

    Intracellular pH plays a significant role in many pathological and physiological processes. A series of quinoline‐pyrene probes were synthesized in one step by oxonium ion triggered alkyne carboamination sequence involving C‐C, C‐O and C‐N bond formation for intracellular pH sensing. Quinoline‐pyrenes showed significant red shift at low pH. The fluorescence lifetime decay measurements of the probe showed decrease in lifetime at pH 4. The probes showed excellent selectivity in the presence of various interfering agents such as amino acids and cations/anions. Furthermore, the probes were found to be completely reversible in the window of pH 4 and 7. Morpholine based quinoline‐pyrene probe efficiently stained lysosomes with high Pearson’s correlation coefficients (0.86) using lysotracker Deep Red DND‐99 as a reference. Co‐localization study of probe with lysotracker DND‐99 showed selective intracellular targeting and shift in fluorescence emission due to acidic lysosomal pH.

    更新日期:2020-01-09
  • Characterization of a Tryptophan 6‐Halogenase from Streptomyces albus and Its Regioselectivity Determinants
    ChemBioChem (IF 2.593) Pub Date : 2020-01-08
    Jeongchan Lee; Joonwon Kim; Hyun Kim; Eun-Jung Kim; Hee-Jin Jeong; Kwon-Young Choi; Byung-Gee Kim

    Tryptophan halogenases are found in diverse organisms and catalyze regiospecific halogenation. They play an important role in biosynthesis of halogenated indole alkaloids, which are biologically active and are of therapeutic importance. Here, a tryptophan 6‐halogenase (SatH) from Streptomyces albus was characterized using a whole‐cell reaction system in Escherichia coli . SatH showed substrate specificity for chloride and bromide ions, leading to regiospecific halogenation at C6 position of L‐tryptophan. In addition, SatH exhibited higher performance in bromination than previously reported tryptophan halogenases in the whole‐cell reaction system. Through structure‐based protein mutagenesis, we revealed that two consecutive residues, A78/V79 in SatH and G77/I78 in PyrH, are one of the key determinants in regioselectivity difference between tryptophan 6‐ and 5‐halogenases. Substituting the AV with GI residues switched the regioselectivity of SatH by moving the orientation of tryptophan. Our data contribute to the understanding of key residues that determine regioselectivity of tryptophan halogenases.

    更新日期:2020-01-09
  • Homogeneous and universal detection of various targets based on dual‐step transduced toehold switch sensor
    ChemBioChem (IF 2.593) Pub Date : 2020-01-08
    Bingling Li; Yidan Tang; Huan Li

    Toehold switch sensors represent a classic of new advances that allow specific targets triggering in‐situ expression of protein reporter. Even if holding unique advantages of label‐free and high portability, they generally require repeated sequence design, high cost and laborious optimization of toehold switch sequence according to different targets. To further simplify the sensing process and improve the practicability, we innovatively introduce a dual‐step pre‐transduction upon traditional toehold switch sensor. Through two successive toehold‐mediated strand displacement reactions, in respective, initiated by linear and associative trigger, different DNAs, RNAs, or ligands of functional nucleic acids can be generally transduced into the input of one well‐performed toehold switch sensor. This advance largely increases the target range. Furthermore, the whole process is signal‐on, homogeneous, and free of any sophisticated operation such as probe labelling, separation, and reconstruction of toehold switch, being even promising and practical in portable or point‐of‐care assays.

    更新日期:2020-01-08
  • N‐Hydroxysuccinimide‐Modified Ethynylphosphonamidates Enable the Synthesis of Configurationally Defined Protein Conjugates
    ChemBioChem (IF 2.593) Pub Date : 2020-01-07
    Marc‐André Kasper; Marcus Gerlach; Anselm F. L. Schneider; Christiane Groneberg; Philipp Ochtrop; Stefanie Boldt; Dominik Schumacher; Jonas Helma; Heinrich Leonhardt; Mathias Christmann; Christian P. R. Hackenberger
    更新日期:2020-01-07
  • Acyldepsipeptide Probes Facilitate Specific Detection of Caseinolytic Protease P Independent of Its Oligomeric and Activity State
    ChemBioChem (IF 2.593) Pub Date : 2020-01-07
    Barbara Eyermann; Maximilian Meixner; Heike Brötz‐Oesterhelt; Iris Antes; Stephan A. Sieber
    更新日期:2020-01-07
  • Using a PCR‐Based Method To Analyze and Model Large, Heterogeneous Populations of DNA
    ChemBioChem (IF 2.593) Pub Date : 2020-01-07
    Helena Andrade; Alvin K. Thomas; Weilin Lin; Francesco V. Reddavide; Yixin Zhang
    更新日期:2020-01-07
  • Asymmetric Reduction of (R)‐Carvone through a Thermostable and Organic‐Solvent‐Tolerant Ene‐Reductase
    ChemBioChem (IF 2.593) Pub Date : 2020-01-07
    Dirk Tischler; Eric Gädke; Daniel Eggerichs; Alvaro Gomez Baraibar; Carolin Mügge; Anika Scholtissek; Caroline E. Paul
    更新日期:2020-01-07
  • Construction and Characterization of a Mirror‐Image l‐DNA i‐Motif
    ChemBioChem (IF 2.593) Pub Date : 2020-01-03
    Yawei Sun; Bo Yang; Yi Hua; Yuanchen Dong; Jianhan Ye; Jiqian Wang; Lijin Xu; Dongsheng Liu
    更新日期:2020-01-04
  • Chemical Methods for N‐ and O‐Sulfation of Small Molecules, Amino Acids and Peptides
    ChemBioChem (IF 2.593) Pub Date : 2020-01-03
    Anna Mary Benedetti; Daniel M. Gill; Chi W. Tsang; Alan M. Jones
    更新日期:2020-01-04
  • Discovery of Ubonodin, an Antimicrobial Lasso Peptide Active against Members of the Burkholderia cepacia Complex
    ChemBioChem (IF 2.593) Pub Date : 2020-01-03
    Wai Ling Cheung‐Lee; Madison E. Parry; Chuhan Zong; Alexis Jaramillo Cartagena; Seth A. Darst; Nancy D. Connell; Riccardo Russo; A. James Link
    更新日期:2020-01-04
  • An expedient synthesis of flexible nucleosides through enzymatic glycosylation of proximal and distal fleximer bases.
    ChemBioChem (IF 2.593) Pub Date : 2020-01-03
    Sophie Vichier-Guerre; Therese Ku; Sylvie Pochet; Katherine L Seley-Radtke

    The structurally unique “fleximer” nucleosides were originally designed to investigate how flexibility in the nucleobase could potentially affect receptor‐ligand recognition and function. Recently they have shown low to sub‐micromolar levels of activity against a number of viruses including coronaviruses, filoviruses and flaviviruses. The synthesis of distal fleximers in particular, has thus far been quite tedious and low yielding. As a potential solution to this issue, a series of proximal fleximer bases (flex‐bases) were successfully coupled to both ribose and 2’‐deoxyribose sugars using the N ‐deoxyribosyltransferase II of Lactobacillus leichmannii ( Ll NDT) and E. coli purine nucleoside phosphorylase (PNP). To explore the range of this facile approach, transglycosylation experiments using a thieno‐expanded tricyclic heterocyclic base, as well as several distal and proximal flex‐bases were performed to determine whether the corresponding fleximer nucleosides could be obtained in this fashion, thus potentially significantly shortening the route to these biologically significant compounds. The results of those studies are reported herein.

    更新日期:2020-01-04
  • BciC‐Catalyzed C132‐Demethoxycarbonylation of Metal Pheophorbide a Alkyl Esters
    ChemBioChem (IF 2.593) Pub Date : 2020-01-03
    Mitsuaki Hirose; Misato Teramura; Jiro Harada; Hitoshi Tamiaki

    Bacteriochlorophyll c molecules self‐aggregate to form large oligomers in the core part of chlorosomes, the main light‐harvesting antenna systems of green photosynthetic bacteria. In the biosynthetic pathway of bacteriochlorophyll c , a BciC enzyme catalyzes the removal of the C13 2 ‐methoxycarbonyl group of chlorophyllide a possessing a free propionate residue at the C17‐position and a magnesium ion as the central metal. The in vitro C13 2 ‐demethoxycarbonylations of chlorophyll a derivatives bearing various alkyl propionate residues and central metals were examined using the BciC enzyme derived from one green sulfur bacteria species, Chlorobaculum tepidum . The BciC enzymatic reactions of zinc pheophorbide a alkyl esters were gradually suppressed with an increase of the alkyl chain length in the C17‐propionate residue (from methyl to pentyl esters) and finally the hexyl ester became inactive for the BciC reaction. Although not only the zinc but also nickel and copper complexes were demethoxycarbonylated by the BciC enzyme, the reactions were largely dependent on the coordination ability of the central metals: Zn > Ni > Cu. The above substrate specificity indicates that the BciC enzyme would not bind directly to the carboxy group of chlorophyllide a , but would bind to its central magnesium to form the stereospecific complex of BciC with chlorophyllide a , giving pyrochlorophyllide a lacking the (13 2 R )‐methoxycarbonyl group.

    更新日期:2020-01-04
  • Strategies to Design and Synthesize Polymer‐Based Stimuli‐Responsive Drug Delivery Nanosystems
    ChemBioChem (IF 2.593) Pub Date : 2019-12-31
    Xing Qin; Yongsheng Li

    The emergence and development of nanomedicine have alleviated the problems existed in traditional chemotherapy drugs, such as short lifetime, concomitant side effects and weak tumor‐targeting capability. Nevertheless, the further applications of drug‐loaded nanocarriers are still limited by their premature leakage, weak targeting capability and insufficient intracellular release. In the past decades, various nanocarriers including gold nanoparticles, porous silica nanoparticles, carbon‐based nanoparticles, micelles, liposomes and polymer‐drug conjugates have been intensively investigated for tumor therapy. Among these, polymer‐based nanocarriers have been paid more attention due to their biocompatibilities and modifiabilities for stimuli‐responsive drug release. In this review, three popular strategies to design and synthesize polymer‐based stimuli‐responsive nanocarriers are discussed. We start our discussion from the stimuli‐responsive polymers with responsive backbones or modified by responsive functional groups for drug encapsulation and release to polymer‐drug conjugates with responsive covalent linkages. Especially, due to the facile synthesis processes and mild reaction conditions of crosslinking structures, the latest progress in responsive crosslinking structures is emphasized. Finally, summary and outlook of these nanomaterials are given, which is expected to provide inspiration for researchers to design more effective and safer tumor‐killing nanomedicines.

    更新日期:2019-12-31
  • Orthogonal Genetic Systems
    ChemBioChem (IF 2.593) Pub Date : 2019-12-30
    John C. Chaput; Piet Herdewijn; Marcel Hollenstein

    Xenobiology is an area of synthetic biology that aims to create model cellular organisms in which the synthetic biology information is encoded in artificial genetic polymers that can replicate alongside natural genetic polymers. This viewpoint discusses the concept of orthogonal genetic polymers and their relationship to natural genetic polymers.

    更新日期:2019-12-31
  • A Quencher‐Free Linear Probe from Serinol Nucleic Acid with a Fluorescent Uracil Analogue
    ChemBioChem (IF 2.593) Pub Date : 2019-12-30
    Keiji Murayama; Hiroyuki Asanuma
    更新日期:2019-12-30
  • Characterisation of the Dynamic Interactions between Complex N‐Glycans and Human CD22
    ChemBioChem (IF 2.593) Pub Date : 2019-12-30
    Cristina Di Carluccio; Enrique Crisman; Yoshiyuki Manabe; Rosa Ester Forgione; Alessandra Lacetera; Jussara Amato; Bruno Pagano; Antonio Randazzo; Angela Zampella; Rosa Lanzetta; Koichi Fukase; Antonio Molinaro; Paul R. Crocker; Sonsoles Martín‐Santamaría; Roberta Marchetti; Alba Silipo
    更新日期:2019-12-30
  • N‐Hydroxysuccinimide‐Modified Ethynylphosphonamidates Enable the Synthesis of Configurationally Defined Protein Conjugates
    ChemBioChem (IF 2.593) Pub Date : 2019-12-30
    Marc‐André Kasper; Marcus Gerlach; Anselm F. L. Schneider; Christiane Groneberg; Philipp Ochtrop; Stefanie Boldt; Dominik Schumacher; Jonas Helma; Heinrich Leonhardt; Mathias Christmann; Christian P. R. Hackenberger
    更新日期:2019-12-30
  • Ascorbate Oxidase Mimetic Activity of Copper(II) Oxide Nanoparticles
    ChemBioChem (IF 2.593) Pub Date : 2019-12-30
    Shao‐Bin He; Ai‐Ling Hu; Quan‐Quan Zhuang; Hua‐Ping Peng; Hao‐Hua Deng; Wei Chen; Guo‐Lin Hong
    更新日期:2019-12-30
  • Phosphine‐Activated Lysine Analogues for Fast Chemical Control of Protein Subcellular Localization and Protein SUMOylation
    ChemBioChem (IF 2.593) Pub Date : 2019-12-30
    Joshua S. Wesalo; Ji Luo; Kunihiko Morihiro; Jihe Liu; Alexander Deiters
    更新日期:2019-12-30
  • 5‐Benzylidene‐4‐Oxazolidinones Are Synergistic with Antibiotics for the Treatment of Staphylococcus aureus Biofilms
    ChemBioChem (IF 2.593) Pub Date : 2019-12-30
    Bram H. Frohock; Jessica M. Gilbertie; Jennifer C. Daiker; Lauren V. Schnabel; Joshua G. Pierce
    更新日期:2019-12-30
  • Preparative and Kinetic Analysis of β‐1,4‐ and β‐1,3‐Glucan Phosphorylases Informs Access to Human Milk Oligosaccharide Fragments and Analogues Thereof
    ChemBioChem (IF 2.593) Pub Date : 2019-12-30
    Ravindra Pal Singh; Giulia Pergolizzi; Sergey A. Nepogodiev; Peterson de Andrade; Sakonwan Kuhaudomlarp; Robert A. Field
    更新日期:2019-12-30
  • Tuning Enzyme Activity for Nonaqueous Solvents: Engineering of an Enantioselective ‘Michaelase’ for Catalysis in High Concentrations of Ethanol
    ChemBioChem (IF 2.593) Pub Date : 2019-12-30
    Chao Guo; Lieuwe Biewenga; Max Lubberink; Ronald van Merkerk; Gerrit J. Poelarends

    Enzymes have evolved to function under aqueous conditions and may not exhibit features essential for biocatalytic application, such as the ability to function in high concentrations of an organic solvent. Consequently, protein engineering is often required to tune an enzyme for catalysis in non‐aqueous solvents. In this study, we have used a collection of nearly all single mutants of 4‐oxalocrotonate tautomerase, which promiscuously catalyzes synthetically useful Michael‐type additions of acetaldehyde to various nitroolefins, to investigate the effect of each mutation on the ability of this enzyme to retain its ‘Michaelase’ activity in elevated concentrations of ethanol. Examination of this mutability landscape allowed the identification of two hotspot positions, Ser‐30 and Ala‐33, at which mutations are beneficial for catalysis in high ethanol concentrations. The ‘hotspot’ position Ala‐33 was then randomized in a highly enantioselective, but ethanol‐sensitive 4‐OT variant (L8F/M45Y/F50A) to generate an improved enzyme variant (L8F/A33I/M45Y/F50A) that showed great ethanol stability and efficiently catalyzes the enantioselective addition of acetaldehyde to nitrostyrene in 40% ethanol (permitting high substrate loading) to give the desired γ‐nitroaldehyde product in excellent isolated yield (89%) and enantiopurity (ee = 98%). The presented work demonstrates the power of mutability‐landscape‐guided enzyme engineering for efficient biocatalysis in non‐aqueous solvents.

    更新日期:2019-12-30
  • Rational‐design engineering to create the flavin reductase variants with thermostable and solvent‐tolerant properties
    ChemBioChem (IF 2.593) Pub Date : 2019-12-30
    Somchart Maenpuen; Vinutsada Pongsupasa; Wiranee Pensook; Piyanuch Anuwan; Napatsorn Kraivisitkul; Chatchadaporn Pinthong; Jittima Phonbuppha; Thikumporn Luanloet; Hein J. Wijma; Marco W. Fraaije; Narin Lawan; Pimchai Chaiyen; Thanyaporn Wongnate; Napatsorn Kraivisitkul

    In this work, we employed computational approaches, FireProt and FRESCO, to predict the thermostable variants of the reductase component (C1) of p‐hydroxyphenylacetate 3‐hydroxylase. Combined with experimental results, two C1 variants; A166L and A58P, were identified as thermotolerant enzymes with their 2.6‐5.6 °C thermostability improvement and increased 2‐3.5‐fold catalytic efficiency. After heat treatment at 45 oC, both of the thermostable C1 variants remain active and generate FMNH‐ for bacterial luciferase and monooxygenase reaction more efficient than wild type (WT). In addition to thermotolerance, A166L and A58P variants exhibited solvent‐tolerant property. The 6‐ns molecular dynamics (MD) simulations at 300‐500 K indicated that mutations of A166 to L and A58 to P resulted in the structural change with increased stabilization of hydrophobic interactions, thus improving thermostability. Our findings demonstrated that the improvement in thermostability of C1 enzyme can lead to the broad‐spectrum uses of C1 as a redox biocatalyst for future industrial applications.

    更新日期:2019-12-30
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