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    Roles of Albumin-binding Proteins in Cancer Progression and Biomimetic Targeted Drug Delivery.
    Chembiochem 2018 Jun 19. Epub 2018 Jun 19.
    CHINA.
    Nutrient transporters have attracted significant attention for their promising application in biomimetic delivery. Due to the active consumption of nutrients, the cancer cells generally overexpress nutrient transporters to meet their increased need for energy and materials. For example, albumin-binding proteins (ABP) are highly overexpressed in the malignant cells, stromal cells, and tumor vessel endothelial cells responsible for albumin uptake. Read More

    Loop protein engineering for improved trans-glycosylation activity of a β-N-acetylhexosaminidase.
    Chembiochem 2018 Jun 17. Epub 2018 Jun 17.
    Technical University of Denmark, Chem. And Biochem. Engineering, Building 229 DTU, 2800, Lyngby, DENMARK.
    Certain enzymes of the glycoside hydrolase family 20 (GH20) exert trans-glycosylation activity catalyzing transfer of β-N-acetylglucosamine (GlcNAc) from a chitobiose donor to lactose to produce lacto-N-triose II (LNT2), a key human milk oligosaccharide backbone moiety. The present work aimed to increase trans-glycosylation activity of two selected hexosaminidases, HEX1 and HEX2, to synthesize LNT2 from lactose and chitobiose. Peptide pattern recognition analysis was used to categorize all GH20 proteins in subgroups. Read More

    Alicyclobacillus acidocaldarius squalene-hopene cyclase: the critical role of the steric bulk at Ala306 and the first enzymatic synthesis of epoxydammarane from 2,3-oxidosqualene.
    Chembiochem 2018 Jun 17. Epub 2018 Jun 17.
    Faculty of Agriculture, Niigata University, Department Applied Biological Chemsitry, Ikarashi 2-8050, Nishi-ku, 950-2181, Niigata, JAPAN.
    The acyclic molecule squalene (1) is cyclized into a 6,6,6,6,5-fused pentacyclic hopene (2) and hopanol (3) (ca. 5:1) by Alicyclobacillus acidocaldarius squalene-hopene cyclase (AaSHC). The polycyclization reaction proceeds with regio- and stereochemical specificity under precise enzymatic control. Read More

    Bacterial Catabolism of Biphenyls. Synthesis and Evaluation of Analogues.
    Chembiochem 2018 Jun 15. Epub 2018 Jun 15.
    University of Innsbruck, AUSTRIA.
    A series of alkylated 2,3-dihydroxybiphenyls (DHBs) have been prepared on gram scale using an effective Directed ortho Metalation (DoM) - Suzuki-Miyaura cross-coupling strategy. These compounds have been used to investigate the substrate specificity of the meta-cleavage dioxygenase BphC, a key enzyme in the microbial catabolism of biphenyl. Isolation and characterization of the meta-cleavage products allows the study of related processes, including the catabolism of lignin-derived biphenyls. Read More

    Improvement of SNAr Reaction Rate by an Electron-withdrawing Group in the Cross-linking of DNA Cytosine-5 Methyltransferase by a Covalent Oligodeoxyribonucleotide Inhibitor.
    Chembiochem 2018 Jun 14. Epub 2018 Jun 14.
    Hokkaido Daigaku, Faculty of Pharmaceutical Sciences, Kita-12, Nishi-6, Kita-ku, 060-0812, Sapporo, JAPAN.
    DNA cytosine 5-methyltransferase (DNMT) catalyzes the methylation at the C5 position of the cytosine residues in the CpG sequence. Aberrant DNA methylation patterns are found in cancer cells. Therefore, inhibition of human DNMT is an effective strategy for treating various cancers. Read More

    Protein Interactions in T7 DNA Replisome Facilitate DNA Damage Bypass.
    Chembiochem 2018 Jun 14. Epub 2018 Jun 14.
    Sichuan University, Public Health Laboratory Sciences and Toxicology, Chengdu, 610041, Chengdu, CHINA.
    DNA replisome inevitably encounters DNA damage during DNA replication. T7 DNA replisome contains DNA polymerase (gp5), the processivity factor thioredoxin (trx), helicase-primase (gp4), and ssDNA binding protein (gp2.5). Read More

    Enhancement of peroxidase activity in the artificial Mimochrome VI catalysts through rational design.
    Chembiochem 2018 Jun 13. Epub 2018 Jun 13.
    University of Napoli "Federico II", Department of Chemical Sciences, Via Cintia, 80126, Napoli, ITALY.
    Rational design provides an attractive strategy to tune and control the reactivity of bioinspired catalysts. While there has been considerable progress in the design of heme oxidase mimetics with active site environments of ever-growing complexity and catalytic efficiency, their stability during turnover is still an open challenge. Here we show that the simple incorporation of two 2-amino isobutyric acids into an artificial peptide-based peroxidase resulted in a new catalyst (FeIII-MC6*a), with higher resistance against oxidative damage, and higher catalytic efficiency. Read More

    An Aminocaprolactam Racemase from Ochrobactrum anthropi with Promiscuous Amino Acid Ester Racemase Activity.
    Chembiochem 2018 Jun 13. Epub 2018 Jun 13.
    GlaxoSmithKline, GSK Medicines Research Centre, Gunnels Wood Road, SG12NY, Stevenage, UNITED KINGDOM.
    The kinetic resolution of amino acid esters (AAEs) is a useful synthetic strategy for the preparation of single enantiomer amino acids. The development of an enzymatic dynamic kinetic resolution (DKR) process for AAEs, which would give a theoretical yield of 100% of the enantiopure product, would require an amino acid ester racemase (AAER), however, no such enzyme has been described. We have identified low AAER activity of 15 U mg-1 in a homolog of a PLP-dependent α-amino ε-caprolactam racemase (ACLR) from Ochrobactrum anthropi. Read More

    Quinoline-glycomimetic conjugates reducing lipogenesis and lipid accumulation in hepatocytes.
    Chembiochem 2018 Jun 13. Epub 2018 Jun 13.
    Indian Institute of Chemical Biology CSIR, Organic and Medicinal Chemistry, 4, Raja S.C Mullick Road, Jadavpur, 700032, Kolkata, INDIA.
    Non-alcoholic fatty liver disease (NAFLD) characterized by excess accumulation of triglyceride in hepatocyte is the major cause of chronic liver disease worldwide and no approved drug is available. The mechanistic target of rapamycin complexes (mTORC) have been implicated to promote lipogenesis and fat accumulation in liver and thus serve as attractive drug targets. Generation of no or low cytotoxic mTOR inhibitors are required as the existing cytotoxic mTOR inhibitors are not useful for NAFLD therapy. Read More

    Capturing and Stabilizing Folded Proteins in Lattices Formed with Branched Oligonucleotide Hybrids.
    Chembiochem 2018 Jun 10. Epub 2018 Jun 10.
    Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569, Stuttgart, Germany.
    The encapsulation of folded proteins in stabilizing matrices is one of the challenges of soft-matter materials science. Capturing such fragile bio-macromolecules from aqueous solution, and embedding them in a lattice that stabilizes them against denaturation and decomposition is difficult. Here, we report that tetrahedral oligonucleotide hybrids as branching elements, and connecting DNA duplexes with sticky ends can assemble into materials. Read More

    Trimethyl Lock - A Multifunctional Molecular Tool for Drug Delivery, Cellular Imaging and Stimuli-responsive Materials.
    Chembiochem 2018 Jun 11. Epub 2018 Jun 11.
    Technische Universität Carolo Wilhelmina zu Braunschweig, Institut for Organic Chemistry, Hagenring 30, Room 240, 38106, Braunschweig, GERMANY.
    Trimethyl lock (TML) systems are based on ortho-hydroxy dihydro cinnamic acid derivatives displaying an increased lactonization reactivity due to unfavorable steric interactions of three pendant methyl groups leading to the formation of hydro coumarins. Protection of the phenolic hydroxy function or masking of the reactivity as benzoquinone derivatives prevents lactonization and provides a trigger for controlled release of molecules attached to the carboxylic acid function via amides, esters or thioesters. Their easy synthesis and possible chemical adaption to several different triggers make TMLs a highly versatile module for the development of drug delivery systems, prodrug approaches, cell imaging tools, molecular tools for supramolecular chemistry as well as smart stimuli-responsive materials. Read More

    Extending the Applicability of Exact Nuclear Overhauser Enhancements to Large Proteins and RNA.
    Chembiochem 2018 Jun 8. Epub 2018 Jun 8.
    University of Colorado Denver One South, Department of Biochemistry and Molecular Genetics, 12801 East 17th Avenue, 80045 , Aurora, UNITED STATES.
    Distance-dependent NOEs are one of the most popular and important experimental restraints for calculating NMR structures. Despite this, they are mostly employed as semi-quantitative upper distance bounds, which discards a wealth of information that is encoded in the cross-relaxation rate constant. Information that is lost includes exact distances between protons and dynamics that occur on the sub-millisecond time-scale. Read More

    Peptides derived from histone 3 and modified at position 18 inhibits histone demethylase KDM6 enzymes.
    Chembiochem 2018 Jun 7. Epub 2018 Jun 7.
    University of Copenhagen, Drug Design and Pharmacology, Jagtvej 162, 2100, Copenhagen, DENMARK.
    The KDM6 subfamily of histone lysine demethylases has recently been implicated as a putative target in treatment of a number of diseases, making the availability of potent and selective inhibitors important. Due to high sequence similarity of the catalytic domain of Jumonji C histone demethylases, development of small molecule family specific inhibitors has, however, proven challenging. One approach to achieve selective inhibition of these enzymes is the use of peptides derived from the substrate the histone H3 C-terminus. Read More

    Special Issue on Optochemical and Optogenetic Control of Cellular Processes.
    Chembiochem 2018 Jun 6;19(12):1198-1200. Epub 2018 Jun 6.
    Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, 15237, USA.
    Diverse optochemical and optobiological approaches are being developed and applied to the light-regulation of cellular processes with exquisite spatial and temporal resolution in cells and multicellular model organisms. In this special issue, experts report some of the latest progress in the expanding field of the optical control of biological systems and present an overview of the state of the art of select approaches. Read More

    Ultrastructural Imaging of Salmonella-Host Interactions Using Super-Resolution Correlative Light-Electron Microscopy of Bioorthogonal Pathogens.
    Chembiochem 2018 Jun 5. Epub 2018 Jun 5.
    Leiden University, Leiden Institute of Chemistry, Gorlaeus Laboratory, Einsteinweg 55, 2333 CC, Leiden, NETHERLANDS.
    The imaging of intracellular pathogens inside host cells is complicated by low resolution and sensitivity of fluorescence microscopy, as well as a lack of ultrastructural information to visualize the pathogens. Here we present a new method to visualize these pathogens during infection that circumvents these problems: by using a metabolic hijacking approach to bioorthogonally label the intracellular pathogen Salmonella Typhimurium, and using these bioorthogonal groups to introduce fluorophores compatible with stochastic optical reconstruction microscopy (STORM), and placing this in a correlative light electron microscopy workflow (CLEM), the pathogen can be imaged within its host cell context Typhimurium with a resolution of 20 nm. This STORM-CLEM approach thus presents a new to understand these pathogens during infection. Read More

    Multicolor fluorescence "click"-chemistry as a means to select membrane targets for pre-targeting approaches by function of their receptor kinetics.
    Chembiochem 2018 Jun 4. Epub 2018 Jun 4.
    Leids Universitair Medisch Centrum, Radiology, Albinusdreef 2, 2300 RC, Leiden, NETHERLANDS.
    Availability of a receptor for theranostic pre-targeting approaches was assessed using a novel "click" chemistry-based de-activatable fluorescence-quenching concept. Efficacy was evaluated in a cell-based model system that exhibits both membranous (available) and internalized (unavailable) receptor-fractions of the clinically relevant receptor chemokine receptor 4 (CXCR4). Proof of concept was based on a de-activatable tracer consisting out of a CXCR4 specific peptide functionalized with a Cy5 dye comprising a chemo-selective azide handle (N3-Cy5-AcTZ14011). Read More

    Enzymatically Ligated DNA-surfactants: Unmasking Hydrophobically Modified DNA for Intracellular Gene Regulation.
    Chembiochem 2018 Jun 3. Epub 2018 Jun 3.
    University of Connecticut, Chemistry, 55 North Eagleville Road, 06269, United States, 06269, Storrs, UNITED STATES.
    Herein we describe the characterization of a novel self-assembling and intracellular disassembling nanomaterial for nucleic acid delivery and targeted gene knockdown. Using a recently developed nucleic acid nanocapsule (NAN) formed from surfactants and conjugated DNAzyme (DNz) ligands, it is shown that the DNz-NAN can enable cellular uptake of the DNAzyme and result in 60% knockdown of a target gene without the use of transfection agents. The DNAzyme also exhibits activity without chemical modification, which we attribute to the underlying nanocapsule design and release of hydrophobically modified nucleic acids as a result of the NANs enzymatically triggered disassembly. Read More

    Diversity-Oriented Synthesis of Diol-Based Peptidomimetics as Potential HIV Protease Inhibitors and Antitumor Agents.
    Chembiochem 2018 Jun 2. Epub 2018 Jun 2.
    Universite Laval, Chemistry, 1045, av de la Medecine, Pavillon Alexandre-Vachon, Chemistry Department, Room VCH-2240D, G1V0A6, Quebec, CANADA.
    Peptidomimetic HIV protease inhibitors are an important class of drugs used in the treatment of AIDS. The synthesis of a new type of diol-based peptidomimetics is described. Our route is flexible, utilises D-hexose as inexpensive starting material and makes minimal use of protection/deprotection cycles. Read More

    Unravelling the relaxed specificity of laminaribiose phosphorylase from Paenibacillus sp. strain YM-1 towards mannose 1-phosphate.
    Chembiochem 2018 Jun 1. Epub 2018 Jun 1.
    UEA, UNITED KINGDOM.
    Glycoside phosphorylases (GPs) carry out a reversible phosphorolysis of carbohydrates into oligosaccharide acceptors and the corresponding sugar 1-phosphates. The reversibility of the reaction enables the use of GPs as biocatalysts for carbohydrate synthesis. Glycosyl hydrolase family 94 (GH94), which only comprises GPs, is one of the most studied GP families that have been used as biocatalysts for carbohydrate synthesis, in academic research and in industrial production. Read More

    Artificial light-regulation of an allosteric bi-enzyme complex by a photosensitive ligand.
    Chembiochem 2018 May 29. Epub 2018 May 29.
    Universit�t Regensburg, Institut f�r Biophysik und physikalische Biochemie, Universit�tsstr. 31, 93053, Regensburg, GERMANY.
    The artificial regulation of proteins by light is an emerging sub-discipline of synthetic biology. Here, we used this concept in order to photo-control both catalysis and allostery within the heterodimeric enzyme complex imidazole glycerol phosphate synthase (ImGP-S). The ImGP-S consists of the cyclase subunit HisF and the glutaminase subunit HisH, which is allosterically stimulated by substrate binding to HisF. Read More

    Coordination-Assisted Bioorthogonal Chemistry: Orthogonal Tetrazine Ligation with Vinylboronic Acid and a Strained Alkene.
    Chembiochem 2018 May 28. Epub 2018 May 28.
    Radboud University, Biomolecular Chemistry, Heyendaalseweg 135, Room HG03.016, 6525AJ, Nijmegen, NETHERLANDS.
    Bioorthogonal chemistry can be used for the selective modification of biomolecules without interfering with any other functionality present. Recent developments in the field provided orthogonal bioorthogonal reactions for modification of multiple biomolecules simultaneously. During our research, we have observed exceptional high reaction rates in the bioorthogonal inverse electron-demand Diels-Alder (iEDDA) reaction between non-strained vinylboronic acids (VBAs) and dipyridyl-s-tetrazines relative to that of tetrazines bearing a methyl or phenyl substituent. Read More

    A glutathione-responsive short sequence of metal-organic complex array.
    Chembiochem 2018 May 28. Epub 2018 May 28.
    National Institute for Materials Science, International Center for Materials Nanoarchitectonics, 1-1 Namiki, 305-0044, Tsukuba, JAPAN.
    A short metal-organic complex array (MOCA 1Cl) containing a sequence of RPtRRu was found to exhibit unique responses to a major bio-thiol glutathione (GSH). Upon binding of GSH to 1Cl, the resultant 1:1 complex (1GS) formed nanofibrous assemblies suggesting its supramolecular polymerization via the double salt-bridge structure formation. The binding behaviors of this MOCA sequence to calf thymus DNA were also GSH dependent, where the larger conformational change of DNA was indicated upon binding with 1GS than 1Cl. Read More

    Discovery of the Tiancilactone Antibiotics by Genome Mining of Atypical Bacterial Type II Diterpene Synthases.
    Chembiochem 2018 May 27. Epub 2018 May 27.
    The Scripps Research Institute, 130 Scripps Way, #3A1, 33458, Jupiter, UNITED STATES.
    While genome mining has advanced the identification, discovery, and study of microbial natural products, discovery of bacterial diterpenoids continues to lag behind. Here we report the identification of 66 putative producers of novel bacterial diterpenoids, and the discovery of the tiancilactone (TNL) family of antibiotics, by genome mining of type II diterpene synthases that do not possess the canonical DXDD motif. The TNLs, broad spectrum antibiotics with moderate activities, were produced by both Streptomyces sp. Read More

    Sesquiterpene Synthase Catalysed Formation of a Novel Medium Sized Cyclic Terpenoid Ether from Farnesyl Diphosphate Analogues.
    Chembiochem 2018 May 26. Epub 2018 May 26.
    UNITED KINGDOM.
    Terpene synthases catalyse the first step in the conversion of prenyl diphosphates to terpenoids. They act as templates for their substrates to generate a reactive conformation, from which a Mg2+-dependent reaction creates a carbocation-PPi ion pair that undergoes a series of rearrangements and (de)protonations to the final terpene product. This tight conformational control was exploited for the (R)-germacrene A synthase and germacradien-4-ol synthase catalysed formation of a medium sized cyclic terpenoid ether from substrates containing nucleophilic functional groups. Read More

    New Insights into the Glycosylation Steps in the Biosynthesis of Sch47554 and Sch47555.
    Chembiochem 2018 May 25. Epub 2018 May 25.
    Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT, 84322, USA.
    Sch47554 and Sch47555 are antifungal compounds from Streptomyces sp. SCC-2136. The availability of the biosynthetic gene cluster made it possible to track genes that encode biosynthetic enzymes responsible for the structural features of these two angucyclines. Read More

    Auroramycin, a potent antibiotic from Streptomyces roseosporus by CRISPR-Cas9 activation.
    Chembiochem 2018 May 25. Epub 2018 May 25.
    SINGAPORE.
    Silent biosynthetic gene clusters represent a potentially rich source for new bioactive compounds. We report the discovery, characterization and biosynthesis of a novel doubly glycosylated 24-membered polyene macrolactam from a silent biosynthetic gene cluster in Streptomyces roseosporus using the CRISPR-Cas9 gene cluster activation strategy. Structural characterization of this polyketide, named auroramycin, revealed a rare isobutyrylmalonyl extender unit and a unique pair of aminosugars. Read More

    Osmium Tag for Posttranscriptionally Modified RNA.
    Chembiochem 2018 May 25. Epub 2018 May 25.
    The University of Tokyo, Research Center for Advanced Science and Technology, 4-6-1 Komaba, Meguro-ku, 153-8904, Tokyo, JAPAN.
    Nucleotide modifications of cellular RNA are highly abundant and diverse, but their origin and functions have not yet been investigated. 5-Methylcytidine (m5C) and 5-methyluridine (m5U) are highly abundant posttranscriptionally modified nucleotides observed in various natural RNAs. Such nucleotides have been labeled through a chemical approach as both undergo oxidation at the C5-C6 double bond, leading to the formation of osmium-bipyridine complexes, which are identified by mass spectrometry. Read More

    Peptide Nucleic Acid Conjugated with Ru-complex Stabilizing Double-Duplex Invasion Complex Even under Physiological Conditions.
    Chembiochem 2018 May 24. Epub 2018 May 24.
    Nagoya University, Graduate School of Science, Furo, Chikusa,, 464-8602, Nagoya, JAPAN.
    Peptide nucleic acid (PNA) can form a stable duplex with DNA, and, accordingly, directly recognize double-stranded DNA through the formation of a double-duplex invasion complex, wherein a pair of complementary PNA strands form two PNA/DNA duplexes. As invasion does not require prior denaturation of DNA, PNA holds great potential for in cellula or in vivo applications. In order to broaden the applicability of PNA invasion, we developed a novel conjugate of PNA with a ruthenium complex. Read More

    Protein Regulation by Intrinsically Disordered Regions: A Role for Subdomains in the IDR of the HIV-1 Rev Protein.
    Chembiochem 2018 May 23. Epub 2018 May 23.
    The Hebrew University of Jerusalem, Institute of Chemistry, Safra Campus, Givat Ram, 91904, Jerusalem, ISRAEL.
    Intrinsically disordered regions (IDRs) in proteins are highly abundant, but they are still commonly viewed as long stretches of polar, solvent accessible residues. Here we show that the disordered C-terminal domain of HIV-1 Rev has two sub-regions that carry out two distinct complementary roles of regulating oligomerization and contributing to stability. We propose this is carried out by a delicate balance between charged and hydrophobic residues within the IDR. Read More

    A Redox-based Superoxide Generation System using Quinone/Quinone Reductase.
    Chembiochem 2018 May 23. Epub 2018 May 23.
    Centre of Biomedical Research, Biocatalysis, SGPGIMS Campus, Raibareli Road, 226014, Lucknow , INDIA.
    Superoxide (O2*-) generation in biological systems is achieved through some of the most complex enzymatic systems. Of these, only the xanthine/xanthine oxidase has been used for in vitro biochemical studies. However, it suffers from limitations such as, lack of suitable heterologous expression system for xanthine oxidase and the irreversible consumption along with low solubility of xanthine under physiological conditions. Read More

    Prolines' fingerprint in intrinsically disordered proteins.
    Chembiochem 2018 May 23. Epub 2018 May 23.
    Universita' degli Studi di Firenze, Department of Chemistry , Department of Chemistry "Ugo Schiff" and Magnetic Resonance Center, Via Luigi Sacconi 6, 50019, Sesto Fiorentino, ITALY.
    NMR spectroscopy is one of the main techniques for high resolution studies of intrinsically disordered proteins (IDPs). Indeed, it permits to map the structural and dynamical features of all the amino acids constituting the polypeptide at atomic resolution. Only proline residues are less straightforward to be characterized, as they lack the amide proton, rendering them not directly visible in the commonly-used 2D ¹H-¹⁵N correlation experiments. Read More

    Synthesis and Characterization of a New Bifunctionalized, Fluorescent and Amphiphilic Molecule to Recruit SH-Containing Molecules to Membranes.
    Chembiochem 2018 May 22. Epub 2018 May 22.
    Humboldt University Berlin, Department of Biology, Invalidenstr. 42, 10115, Berlin, GERMANY.
    The present study describes the synthesis and characterization of an amphiphilic construct which is aimed to recruit SH-containing molecules to membranes. The construct consists of (i) an aliphatic chain to enable the anchoring within membranes, (ii) a maleimide moiety to react with the sulfhydryl group of a soluble (bio)molecule, and (iii) a fluorescence moiety to follow the construct by fluorescence spectroscopy and microscopy. It is shown, that the construct can be incorporated into preformed membranes allowing the application of the approach with biological membranes. Read More

    Evidence for the Formation of a Radical-Mediated Flavin-N5 Covalent Intermediate.
    Chembiochem 2018 May 18. Epub 2018 May 18.
    Department of Biochemistry and Center for Drug Discovery, Virginia Tech, 360 West Campus Drive, Blacksburg, VA, 24061, USA.
    The redox-neutral reaction catalyzed by 2-haloacrylate hydratase (2-HAH) leads to the conversion of 2-chloroacrylate to pyruvate. Previous mechanistic studies demonstrated the formation of a flavin-iminium ion as an important intermediate in the 2-HAH catalytic cycle. Time-resolved flavin absorbance studies were performed in this study, and the data showed that the enzyme is capable of stabilizing both anionic and neutral flavin semiquinone species. Read More

    A Photoactivatable α β -Specific Integrin Ligand.
    Chembiochem 2018 Jun 30;19(12):1280-1287. Epub 2018 May 30.
    INM-Leibniz Institute for New Materials, Campus D2 2, 66123, Saarbrücken, Germany.
    The integrin α β is overexpressed in colon, breast, ovarian, lung and brain tumours, and has been identified as key component in mechanosensing. In order to study how dynamic changes in α β engagement affect cellular behaviour, photoactivatable derivatives of α β -specific ligands are presented in this article. A photoremovable protecting group (PRPG) was introduced into the ligand structure at a relevant position for integrin recognition. Read More

    Transition metal ions mediated tyrosine based short peptide amphiphile nanostructures inhibit bacterial growth.
    Chembiochem 2018 May 17. Epub 2018 May 17.
    Dr. Harisingh Gour Central University, Diatom Nanoengineering and metabolism lab (DNM), School of Applied Sciences, Department of Criminology and Forensic Science, 470003, SAGAR, INDIA.
    We report the design and synthesis of biocompatible small peptide based molecule for the controlled and targeted delivery of the encapsulated bioactive metal ions via transforming their internal nanostructures. Tyrosine based short peptide amphiphile (sPA) was synthesized which self-assembled into β-sheet like secondary structures. The self assembly of the designed sPA was modulated by using different bioactive transition metal ions which is confirmed by spectroscopic and microscopic techniques. Read More

    Cyclic Peptides for Efficient Detection of Collagen.
    Chembiochem 2018 May 14. Epub 2018 May 14.
    Waseda University, Department of Chemistry and Biochemistry, 3-4-1 Okubo, Shinjuku-ku, 169-8555, Tokyo, JAPAN.
    We report here a novel class of collagen-binding peptides, cyclic collagen-mimetic peptides (cCMPs), which efficiently hybridize with triple helix-forming portions of collagen. cCMPs are composed of two parallel collagen-like (Xaa-Yaa-Gly)n strands with both termini tethered by covalent linkages. Enzyme-linked immunosorbent assay and western blotting analysis showed that cCMPs exhibit more potent affinity toward collagen than reported collagen-binding peptides and specifically detect different collagen polypeptides in a mixture of proteins. Read More

    Designed Enzyme Promotes Selective Post-translational Acylation.
    Chembiochem 2018 May 13. Epub 2018 May 13.
    Syracuse University, Chemistry, 111 College Place, 13244, Syracuse, UNITED STATES.
    A computationally designed allosterically regulated catalyst (CaM M144H) produced by substituting a single residue in calmodulin, a non-enzymatic protein, is capable of efficient and site selective post-translational acylation of lysines in peptides with highly diverse sequences. Calmodulin binding partners are involved in regulating a large number of cellular processes, this new chemical biology tool will help identify them and provide structural insight into their interactions with calmodulin. Read More

    A Defined and Flexible Pocket Explains Aryl Substrate Promiscuity by the Cahuitamycin Starter Unit Activating Enzyme CahJ.
    Chembiochem 2018 May 9. Epub 2018 May 9.
    UNITED STATES.
    Cahuitamycins are biofilm inhibitors biosynthesized by a convergent NRPS pathway. Previous genetic analysis indicated that a discrete enzyme, CahJ, serves as a gatekeeper for cahuitamycin structural diversification. Herein, the CahJ protein was probed structurally, functionally and through mutasynthesis. Read More

    Profiling the Nucleobase and Structure Selectivity of Anticancer Drugs and other DNA Alkylating Agents by RNA Sequencing.
    Chembiochem 2018 May 6. Epub 2018 May 6.
    Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056, Basel, Switzerland.
    Drugs that covalently modify DNA are components of most chemotherapy regimens, often serving as first-line treatments. Classically, the reactivity and selectivity of DNA alkylating agents has been determined in vitro with short oligonucleotides. A statistically sound analysis of sequence preferences of alkylating agents is untenable with serial analysis methods because of the combinatorial explosion of sequence possibilities. Read More

    Conformation Analysis of GalNAc-Appended Sugar Amino Acid Foldamers as Glycopeptide Mimics.
    Chembiochem 2018 May 4. Epub 2018 May 4.
    Centre for Nuclear Magnetic Resonance, SAIF, CSIR-Central Drug Research Institute, Lucknow, 226031, India.
    Sugar amino acid (SAA)-based foldamers with well-defined secondary structures were appended with N-acetylgalactosamine (GalNAc) sugars to access sequence-defined, multidentate glycoconjugates with full control over number, spacing and position. Conformation analysis of these glycopeptides by extensive NMR spectroscopic studies revealed that the appended GalNAc units had a profound influence on the native conformational behaviour of the SAA foldamers. Whereas the 2,5-cis glycoconjugate showed a helical structure in water, comprising of two consecutive 16-membered hydrogen bonds, its 2,5-trans congener displayed an unprecedented 16/10-mixed turn structure not seen before in any glycopeptide foldamer. Read More

    Single-Turnover Kinetics Reveal a Distinct Mode of Thiamine Diphosphate-Dependent Catalysis in Vitamin K Biosynthesis.
    Chembiochem 2018 May 3. Epub 2018 May 3.
    Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
    MenD, or (1R,2S,5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC) synthase, uses a thiamine diphosphate (ThDP)-dependent tetrahedral Breslow intermediate rather than a canonical enamine for catalysis in the biosynthesis of vitamin K. By real-time monitoring of the cofactor chemical state with circular dichroism spectroscopy, we found that a new post-decarboxylation intermediate was formed from a multistep process that was rate limited by binding of the α-ketoglutarate substrate before it quickly relaxed to the characterized tetrahedral Breslow intermediate. In addition, the chemical steps leading to the reactive post-decarboxylation intermediates were not affected by the electrophilic substrate, isochorismate, whereas release of the product was found to limit the whole catalytic process. Read More

    Structural Insight into the Allosteric Coupling of Cu1 Site and Trinuclear Cu Cluster in CotA Laccase.
    Chembiochem 2018 May 3. Epub 2018 May 3.
    Key Laboratory of Environmental and Applied Microbiology, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, P.R. China.
    In laccase, type 1 copper (Cu1) was connected to the trinuclear copper center (TNC) by the conserved Cys-His bridge. An allosteric coupling between the two redox sites has been reported; however, the molecular mechanism underlining the allosteric coupling is unknown. In this study, ligands of the two type 3 copper sites, including His491 and His493, in CotA were mutated to Cys or Ala. Read More

    The Alkylquinolone Repertoire of Pseudomonas aeruginosa is linked to Structural Flexibility of the FabH-like PQS Biosynthesis Enzyme PqsBC.
    Chembiochem 2018 May 3. Epub 2018 May 3.
    Helmholtz Centre for Infection Research, Structure and Function of Proteins, Inhoffenstr. 7, 38124, Braunschweig, GERMANY.
    Pseudomonas aeruginosa is a bacterial pathogen that causes life-threatening infections in immunocompromised patients. It produces a large armory of saturated and mono-unsaturated 2-alkyl-4(1H)-quinolones (AQs) or AQ N-oxides (AQNOs) that serve as signaling molecules to control the production of virulence factors, are involved in membrane vesicle formation and iron chelation and also have e.g. Read More

    Preparation of Cyclic Prodiginines by Mutasynthesis in Pseudomonas putida KT2440.
    Chembiochem 2018 May 2. Epub 2018 May 2.
    Institute of Bioorganic Chemistry, Heinrich Heine University Düsseldorf located at Forschungszentrum Jülich, Stetternicher Forst, Building 15.8, 52426, Jülich, Germany.
    Prodiginines are a group of naturally occurring pyrrole alkaloids produced by various microorganisms and known for their broad biological activities. The production of nature-inspired cyclic prodiginines was enabled by combining organic synthesis with a mutasynthesis approach based on the GRAS (generally recognized as safe) certified host strain Pseudomonas putida KT2440. The newly prepared prodiginines exerted antimicrobial effects against relevant alternative biotechnological microbial hosts whereas P. Read More

    A Carbapenem-Based Off-On Fluorescent Probe for Specific Detection of Metallo-β-Lactamase Activities.
    Chembiochem 2018 May 2. Epub 2018 May 2.
    State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, P.R. China.
    Metallo-β-lactamase is one of the major clinical threats because this β-lactam-hydrolyzing enzyme confers significant resistance to most β-lactam antibiotics, including carbapenems, among bacterial pathogens. Reported herein is a novel fluorogenic sensor for the specific detection of metallo-β-lactamase activities. This carbapenem-based reagent exhibits excellent selectivity to metallo-β-lactamase over other serine-β-lactamases, including serine carbapenemases. Read More

    Heterologous Biosynthesis of Fungal Indole Sesquiterpene Sespendole.
    Chembiochem 2018 May 2. Epub 2018 May 2.
    Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo, 060-0810, Japan.
    Indole sesquiterpene sespendole, which has been isolated from the filamentous fungus Pseudobotrytis terrestris FKA-25, is a specific inhibitor of lipid droplet synthesis in mouse macrophages. The biosynthetic pathway that involves genes encoding six enzymes (spdEMBQHJ) was elucidated through heterologous expression of spd genes in Aspergillus oryzae, biotransformation experiments, and in vitro enzymatic reactions with a recombinant protein, thereby revealing the mechanism underlying the characteristic modification on the indole ring, catalyzed by a set of prenyltransferase (SpdE)/cytochrome P450 (SpdJ) enzymes. Functional analysis of the homologous genes encoding these enzymes involved in the biosynthesis of lolitrem allowed a biosynthetic pathway for the bicyclic ring skeleton fused to the indole ring to be proposed. Read More

    The Photo-Physics of Polythiophene Nanoparticles for Biological Applications.
    Chembiochem 2018 May 1. Epub 2018 May 1.
    Center for Nano Science and Technology, IIT@PoliMI, Via Pascoli 70/3, 20133, MIlano, ITALY.
    In this work the photo-physics of poly(3-hexyltiophene) nanoparticles (NPs) is investigated in the context of their biological applications. The NPs made as colloidal suspensions in aqueous buffers present a distinct absorption band in the low energy region. Based on systematic analysis of absorption and transient absorption spectra taken under different pH conditions, this band is associated to charge transfer states generated by the polarization of loosely bound polymer chains and originated from complexes formed with electron withdrawing species. Read More

    A Comparative Reengineering Study of cpADH5 through Iterative and Simultaneous Multisite Saturation Mutagenesis.
    Chembiochem 2018 Apr 30. Epub 2018 Apr 30.
    Lehrstuhl für Biotechnologie, RWTH Aachen University, Worringerweg 3, 52074, Aachen, Germany.
    Positions identified in directed evolution campaigns or by (semi)rational design can be recombined iteratively or simultaneously. Iterative recombination has yielded many success stories and is beneficially used if screening capabilities are limited (four iterative SSMs generate 20×4=80 different enzyme variants). Simultaneous site saturation mutagenesis offers significantly higher diversity (20 =160 000 variants) and enables greater improvements to be found, especially if the selected positions are in close proximity to each other (cooperative effects). Read More

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