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991.
Capt. Courtney Kiggins Austin Skinner Prof. Marino J. E. Resendiz 《Chembiochem : a European journal of chemical biology》2020,21(9):1347-1355
Aptamers are attractive constructs due to their high affinity/selectivity towards a target. Here 7,8-dihydro-8-oxoguanosine (8-oxoG) has been used, due in part to its unique H-bonding capabilities (Watson–Crick or Hoogsteen), to expand the “RNA alphabet”. Its impact on the theophylline RNA aptamer was explored by modifying its binding pocket at positions G11, G25, or G26. Structural probing, with RNases A and T1, showed that modification at G11 leads to a drastic structural change, whereas the G25-/G26-modified analogues exhibited cleavage patterns similar to that of the canonical construct. The recognition properties towards three xanthine derivatives were then explored through thermophoresis. Modifying the aptamer at position G11 led to binding inhibition. Modification at G25, however, changed the selectivity towards theobromine (Kd≈160 μm ), with a poor affinity for theophylline (Kd>1.5 mm ) being observed. Overall, 8-oxoG can have an impact on the structures of aptamers in a position-dependent manner, leading to altered target selectivity. 相似文献
992.
Wai Ling Cheung-Lee Madison E. Parry Dr. Chuhan Zong Alexis Jaramillo Cartagena Prof. Seth A. Darst Prof. Nancy D. Connell Dr. Riccardo Russo Prof. A. James Link 《Chembiochem : a European journal of chemical biology》2020,21(9):1335-1340
We report the heterologous expression, structure, and antimicrobial activity of a lasso peptide, ubonodin, encoded in the genome of Burkholderia ubonensis. The topology of ubonodin is unprecedented amongst lasso peptides, with 18 of its 28 amino acids found in the mechanically bonded loop segment. Ubonodin inhibits RNA polymerase in vitro and has potent antimicrobial activity against several pathogenic members of the Burkholderia genus, most notably B. cepacia and B. multivorans, causative agents of lung infections in cystic fibrosis patients. 相似文献
993.
Dr. Dandan Li Qianqian Guo Liming Ding Wei Zhang Lu Cheng Yanqiu Wang Dr. Zhuobin Xu Dr. Huihui Wang Prof. Lizeng Gao 《Chembiochem : a European journal of chemical biology》2020,21(18):2620-2627
Peroxidase-mimicking nanozymes that can generate toxic hydroxyl radicals (.OH) hold great promise as antibacterial alternatives. However, most of them display optimal performance under strongly acidic conditions (pH 3–4), and are thus not feasible for many medical uses, including burn infections with a wound pH close to neutral. Herein, we report a copper-based nanozyme (CuCo2S4) that exhibits intrinsic peroxidase-like activity and can convert H2O2 into .OH at neutral pH. In particular, bimetallic CuCo2S4 nanoparticles (NPs) exhibited enhanced peroxidase-like activity and antibacterial capacity, superior to that of the corresponding monometallic CuS and CoS NPs. The CuCo2S4 nanozymes possessed excellent ability to kill various bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, this CuCo2S4 nanozymes could effectively disrupt MRSA biofilms in vitro and accelerate MRSA-infected burn healing in vivo. This work provides a new peroxidase mimic to combat bacteria in neutral pH milieu and this CuCo2S4 nanozyme could be a promising antibacterial agent for the treatment of burn infections. 相似文献
994.
Angela Sester Katrin Stüer-Patowsky Prof. Dr. Wolf Hiller Dr. Florian Kloss Prof. Dr. Stephan Lütz Prof. Dr. Markus Nett 《Chembiochem : a European journal of chemical biology》2020,21(16):2268-2273
Enzyme promiscuity has important implications in the field of biocatalysis. In some cases, structural analogues of simple metabolic building blocks can be processed through entire pathways to give natural product derivatives that are not readily accessible by chemical means. In this study, we explored the plasticity of the aurachin biosynthesis pathway with regard to using fluoro- and chloroanthranilic acids, which are not abundant in the bacterial producers of these quinolone antibiotics. The incorporation rates of the tested precursor molecules disclosed a regiopreference for halogen substitution as well as steric limitations of enzymatic substrate tolerance. Three previously undescribed fluorinated aurachin derivatives were produced in preparative amounts by fermentation and structurally characterized. Furthermore, their antibacterial activities were evaluated in comparison to their natural congener aurachin D. 相似文献
995.
Dr. Guangze Yang Dr. Yun Liu Song Jin Prof. Chun-Xia Zhao 《Chembiochem : a European journal of chemical biology》2020,21(20):2871-2879
Among various drug-delivery systems, core-shell nanoparticles have many advantages. Inspired by nature, biomimetic synthesis has emerged as a new strategy for making core-shell nanoparticles in recent years. Biomimetic mineralization is the process by which living organisms produce minerals based on biomolecule templating that leads to the formation of hierarchically structured organic–inorganic materials. In this minireview, we mainly focus on the synthesis of core-shell nanoparticle drug-delivery systems by biomimetic mineralization. We review various biomimetic mineralization methods for fabricating core-shell nanoparticles including silica-based, calcium-based and other nanoparticles, and their applications in drug delivery. We also summarize strategies for drug loading in the biomolecule-mineralized core-shell NPs. Current challenges and future directions are also discussed. 相似文献
996.
Dr. Liam J. Stephens Dr. Aviva Levina Dr. Iman Trinh Dr. Victoria L. Blair Dr. Melissa V. Werrett Prof. Peter A. Lay Prof. Philip C. Andrews 《Chembiochem : a European journal of chemical biology》2020,21(8):1188-1200
RuII-arene complexes provide a versatile scaffold for novel anticancer drugs. Seven new RuII-arene-thiocarboxylato dimers were synthesized and characterized. Three of the complexes ( 2 a , b and 5 ) showed promising antiproliferative activities in MDA-MB-231 (human invasive breast cancer) cells, and were further tested in a panel of fifteen cancerous and noncancerous cell lines. Complex 5 showed moderate but remarkably selective activity in MDA-MB-231 cells (IC50=39±4 μm Ru). Real-time proliferation studies showed that 5 induced apoptosis in MDA-MB-231 cells but had no effect in A549 (human lung cancer, epithelial) cells. By contrast, 2 a and b showed moderate antiproliferative activity, but no apoptosis, in either cell line. Selective cytotoxicity of 5 in aggressive, mesenchymal-like MDA-MB-231 cells over many common epithelial cancer cell lines (including noninvasive breast cancer MCF-7) makes it an attractive lead compound for the development of specifically antimetastatic Ru complexes with low systemic toxicity. 相似文献
997.
Poya Kavianpour Madeleine C. M. Gemmell Dr. Jan U. Kahlert Prof. Louis M. Rendina 《Chembiochem : a European journal of chemical biology》2020,21(19):2786-2791
Histone deacetylase enzymes (HDACs) are responsible for the global silencing of tumour-suppressor genes. Treatment with a histone deacetylase inhibitor (HDACi) can reverse this process and restore normal cell function. Herein, we report a small series of boron-based (boronic acid, boronate ester and closo-1,2-carborane) HDAC2 inhibitors with IC50 values in the nanomolar range. The boronate ester 4 b was the most potent compound assessed in this study (IC50=40.6±1.5 nM), followed closely by the 1,2-closo-carborane (IC50=42.9±1.5 nM). Compound 4 b exceeds the potency of the related gold-standard HDAC pan-inhibitor vorinostat ( 1 ) toward this particular HDAC isoform. 相似文献
998.
Yuanfang Tao Xin Ji Dr. Jian Zhang Yue Jin Nannan Wang Prof. Yubing Si Prof. Weili Zhao 《Chembiochem : a European journal of chemical biology》2020,21(21):3131-3136
Near-infrared (NIR) fluorescent probes are very significant for detecting cysteine in biological systems. Herein, we report a highly selective and sensitive NIR turn-on fluorescent probe (BDP-NIR) based on BODIPY with large Stokes shift (105 nm) for detecting Cys. We clarified the sensing mechanism based on the different thiol-induced SNAr substitution/rearrangement reaction of the probe with cysteine and homocysteine/glutathione, which leads to the corresponding amino- and thiol-BODIPY dyes with distinct photophysical properties. Moreover, a novel mechanism of fluorescence quenching was demonstrated by density functional theory calculation. The reason for the fluorescence quenching of the probe might be intersystem crossing (from singlet to triplet excited state). Moreover, BDP-NIR had a high linear dynamic range of 0–500 μM, which was promising for detecting cysteine quantificationally. Significantly, BDP-NIR was capable of sensing endogenous cysteine in living cells and in vivo. 相似文献
999.
Nicolas Dolder Prof. Dr. Christoph von Ballmoos 《Chembiochem : a European journal of chemical biology》2020,21(15):2219-2224
Enzyme-mediated proton transport across biological membranes is critical for many vital cellular processes. pH-sensitive fluorescent dyes are an indispensable tool for investigating the molecular mechanism of proton-translocating enzymes. Here, we present a novel strategy to entrap pH-sensitive probes in the lumen of liposomes that has several advantages over the use of soluble or lipid-coupled probes. In our approach, the pH sensor is linked to a DNA oligomer with a sequence complementary to a second oligomer modified with a lipophilic moiety that anchors the DNA conjugate to the inner and outer leaflets of the lipid bilayer. The use of DNA as a scaffold allows subsequent selective enzymatic removal of the probe in the outer bilayer leaflet. The method shows a high yield of insertion and is compatible with reconstitution of membrane proteins by different methods. The usefulness of the conjugate for time-resolved proton pumping measurements was demonstrated by using two large membrane protein complexes. 相似文献
1000.
Pooja Kaur Dr. Alice Johnson Joshua Northcote-Smith Dr. Chunxin Lu Dr. Kogularamanan Suntharalingam 《Chembiochem : a European journal of chemical biology》2020,21(24):3618-3624
Immunogenic cell death (ICD) offers a method of stimulating the immune system to attack and remove cancer cells. We report a copper(II) complex containing a Schiff base ligand and a polypyridyl ligand, 4 , capable of inducing ICD in breast cancer stem cells (CSCs). Complex 4 kills both bulk breast cancer cells and breast CSCs at sub-micromolar concentrations. Notably, 4 exhibits greater potency (one order of magnitude) towards breast CSCs than salinomycin (an established breast CSC-potent agent) and cisplatin (a clinically approved anticancer drug). Epithelial spheroid studies show that 4 is able to selectively inhibit breast CSC-enriched HMLER-shEcad spheroid formation and viability over non-tumorigenic breast MCF10 A spheroids. Mechanistic studies show that 4 operates as a Type II ICD inducer. Specifically, 4 readily enters the endoplasmic reticulum (ER) of breast CSCs, elevates intracellular reactive oxygen species (ROS) levels, induces ER stress, evokes damage-associated molecular patterns (DAMPs), and promotes breast CSC phagocytosis by macrophages. As far as we are aware, 4 is the first metal complex to induce ICD in breast CSCs and promote their engulfment by immune cells. 相似文献