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https://www.readbyqxmd.com/read/29910943/self-resistance-guided-genome-mining-uncovers-new-topoisomerase-inhibitors-from-myxobacteria
#1
Fabian Panter, Daniel Krug, Sascha Baumann, Rolf Müller
There is astounding discrepancy between the genome-inscribed production capacity and the set of known secondary metabolite classes from many microorganisms as detected under laboratory cultivation conditions. Genome-mining techniques are meant to fill this gap, but in order to favor discovery of structurally novel as well as bioactive compounds it is crucial to amend genomics-based strategies with selective filtering principles. In this study, we followed a self-resistance guided approach aiming at the discovery of inhibitors of topoisomerase, known as valid target in both cancer and antibiotic therapy...
June 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29890217/a-novel-caspase-6-from-sea-cucumber-holothuria-leucospilota-molecular-characterization-expression-analysis-and-apoptosis-detection
#2
Aifen Yan, Chunhua Ren, Ting Chen, Da Huo, Xiao Jiang, Hongyan Sun, Chaoqun Hu
In this study, a novel caspase-6 named HLcaspase-6 was identified from sea cucumber Holothuria leucospilota. The full-length cDNA of HLcaspase-6 is 2195 bp in size, containing a 126 bp 5'-untranslated region (UTR), a 1043 bp 3'-UTR and a 1026 bp open reading frame (ORF) encoding a protein of 341 amino acids with a deduced molecular weight of 38.57 kDa. HLcaspase-6 contains the common signatures of the caspase family, including the conserved pentapeptide motif QACRG, as well as the P20 and P10 domains. In addition, HLcaspase-6 contains a short pro-domain...
June 8, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29888777/rational-design-of-an-anchoring-peptide-for-high-efficiency-and-quantitative-modification-of-peptides-and-dna-strands-on-gold-nanoparticles
#3
Xin-Yi Li, Fu-Yan Feng, Xiao-Dong Zhou, Ji-Ming Hu
The pentapeptide Cys-Ala-Leu-Asn-Asn (CALNN) could stabilize gold nanoparticles (AuNPs), most of which serve as anchoring blocks for various bioanalyses by introducing recognition blocks. However, the typical conjugation strategy greatly suffers from excessive use of peptides, overnight incubation and consequently low efficiency. In this study, new design criteria for the efficacious anchor were established. In addition, a stable, instantaneous and effective modification of the anchoring peptide RRFPDD or its derivatives on AuNPs is first proposed for the first time...
June 11, 2018: Nanoscale
https://www.readbyqxmd.com/read/29886279/impact-of-the-green-tea-ingredient-epigallocatechin-gallate-and-a-short-pentapeptide-ile-ile-ala-glu-lys-on-the-structural-organization-of-mixed-micelles-and-the-related-uptake-of-cholesterol
#4
Francesco Giangreco, Siegfried Höfinger, Evangelos Bakalis, Francesco Zerbetto
BACKGROUND: High levels of blood cholesterol are conventionally linked to an increased risk of developing cardiovascular disease (Grundy, 1986). Here we examine the molecular mode of action of natural products with known cholesterol-lowering activity, such as for example the green tea ingredient epigallocatechin gallate and a short pentapeptide, Ile-Ile-Ala-Glu-Lys. METHODS: Molecular Dynamics simulations are used to gain insight into the formation process of mixed micelles and, correspondingly, how active agents epigallocatechin gallate and Ile-Ile-Ala-Glu-Lys could possibly interfere with it...
June 7, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29885610/enzyme-structures-of-the-bacterial-peptidoglycan-and-wall-teichoic-acid-biogenesis-pathways
#5
REVIEW
Nathanael A Caveney, Franco Kk Li, Natalie Cj Strynadka
The bacterial cell wall is a complex polymeric structure with essential roles in defence, survival and pathogenesis. Common to both Gram-positive and Gram-negative bacteria is the mesh-like peptidoglycan sacculus that surrounds the outer leaflet of the cytoplasmic membrane. Recent crystallographic studies of enzymes that comprise the peptidoglycan biosynthetic pathway have led to significant new understanding of all stages. These include initial multi-step cytosolic formation of sugar-pentapeptide precursors, transfer of the precursors to activated polyprenyl lipids at the membrane inner leaflet and flippase mediated relocalization of the resulting lipid II precursors to the outer leaflet where glycopolymerization and subsequent peptide crosslinking are finalized...
June 6, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29885033/ancient-association-of-cyanobacterial-multicellularity-with-the-regulator-hetr-and-an-rgsgr-pentapeptide-containing-protein-patx
#6
Jeff Elhai, Ivan Khudyakov
One simple model to explain biological pattern postulates the existence of a stationary regulator of differentiation that positively affects its own expression, coupled with a diffusible suppressor of differentiation that inhibits the regulator's expression. The first has been identified in the filamentous, heterocyst-forming cyanobacterium, Anabaena PCC 7120 as the transcriptional regulator, HetR, and the second as the small protein, PatS, which contains a critical RGSGR motif that binds to HetR. HetR is present in almost all filamentous cyanobacteria, but only a subset of heterocyst-forming strains carry proteins similar to PatS...
June 8, 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29883565/supramolecular-nanoparticles-of-insulin-and-pentapeptide-for-inhibition-of-fibrillation-and-controlled-release
#7
Anna Zhou, Jing Xie, Honghua Han, Yantao Chen, Changsheng Zhao, Jianshu Li
Despite their obvious advantages of making insulin injections less frequent and reducing discomfort for diabetic patients, various controlled release formulations of insulin still have some problems caused by the fibrillation of protein. Here, we demonstrate that pentapeptide FVPRK inspired from the C-terminal of the insulin receptor α-CT can form supramolecularassembled nanoparticles with insulin, showing a controlled release of insulin and an inhibition effect of insulin fibrillation. These nanoparticles were proved non-toxic through cytotoxicity study and the assembling mechanisms was explored by computer simulations, indicating that the strong π-π interaction between C-terminus of insulin B-chain and Phe of the pentapeptide may provide the corresponding driving force...
May 1, 2018: Journal of Biomedical Nanotechnology
https://www.readbyqxmd.com/read/29859368/a-dual-targeting-reconstituted-high-density-lipoprotein-leveraging-the-synergy-of-sorafenib-and-antimirna21-for-enhanced-hepatocellular-carcinoma-therapy
#8
Min Li, Yujie Su, Fangrong Zhang, Kerong Chen, Xiangting Xu, Lin Xu, Jianping Zhou, Wei Wang
Sorafenib (So) is a multi-target kinase inhibitor extensively used in clinic for hepatocellular carcinoma therapy. It demonstrated strong inhibition both in tumor proliferation and tumor angiogenesis, while hampered by associated cutaneous side-effect and drug resistance. The knockdown of miR-21 with antisense oligonucleotides (antimiRNA21) was regarded as an efficient strategy for increasing tumor sensibility to chemotherapy, which could be employed to appreciate the efficacy of So. Herein, we successfully formulated a dual-targeting delivery system for enhanced hepatocellular carcinoma therapy by encapsulating So and antimiRNA21 in RGD pentapeptide-modified reconstituted high-density lipoprotein (RGD-rHDL/So/antimiRNA21)...
May 30, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29786738/design-and-mechanistic-study-of-a-novel-gold-nanocluster-based-drug-delivery-system
#9
Qinzhen Li, Yiting Pan, Tiankai Chen, Yuanxin Du, Honghua Ge, Buchang Zhang, Jianping Xie, Haizhu Yu, Manzhou Zhu
Chemically-triggered drug delivery systems (DDSs) have been extensively studied as they do not require specialized equipment to deliver the drug and can deeply penetrate human tissue. However, their syntheses are complicated and they tend to be cytotoxic, which restricts their clinical utility. In this work, the self-regulated drug loading and release capabilities of peptide-protected gold nanoclusters (Pep-Au NCs) are investigated using vancomycin (Van) as the model drug. Gold nanoclusters (Au NCs) coated with a custom-designed pentapeptide are synthesized as drug delivery nanocarriers and loaded with Van - a spontaneous process reliant on the specific binding between Van and the custom-designed peptide...
May 22, 2018: Nanoscale
https://www.readbyqxmd.com/read/29782819/analytical-performance-of-an-immunoassay-to-measure-proenkephalin
#10
Leslie J Donato, Jeffrey W Meeusen, John C Lieske, Deborah Bergmann, Andrea Sparwaßer, Allan S Jaffe
BACKGROUND: Endogenous opioids, enkephalins, are known to increase with acute kidney injury. Since the mature pentapeptides are unstable, we evaluated the performance of an assay that measures proenkephalin 119-159 (PENK), a stable peptide formed concomitantly with mature enkephalins. METHODS: PENK assay performance was evaluated on two microtiterplate/chemiluminescence sandwich immunoassay formats that required 18 or 1 h incubation times. PENK concentration was measured in plasma from healthy individuals to establish a reference interval and in patients with varied levels of kidney function and comorbidities to assess the association with measured glomerular filtration rate (mGFR) using iothalamate clearance...
May 18, 2018: Clinical Biochemistry
https://www.readbyqxmd.com/read/29780540/the-cycloaspeptides-uncovering-a-new-model-for-methylated-nonribosomal-peptide-biosynthesis
#11
Kate M J de Mattos-Shipley, Claudio Greco, David M Heard, Gemma Hough, Nicholas P Mulholland, Jason L Vincent, Jason Micklefield, Thomas J Simpson, Christine L Willis, Russell J Cox, Andrew M Bailey
The cycloaspeptides are bioactive pentapeptides produced by various filamentous fungi, which have garnered interest from the agricultural industry due to the reported insecticidal activity of the minor metabolite, cycloaspeptide E. Genome sequencing, bioinformatics and heterologous expression confirmed that the cycloaspeptide gene cluster contains a minimal 5-module nonribosomal peptide synthetase (NRPS) and a new type of trans -acting N -methyltransferase ( N -MeT). Deletion of the N -MeT encoding gene and subsequent feeding studies determined that two modules of the NRPS preferentially accept and incorporate N -methylated amino acids...
May 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29778697/structural-basis-for-selective-inhibition-of-antibacterial-target-mray-a-membrane-bound-enzyme-involved-in-peptidoglycan-synthesis
#12
REVIEW
Jenny Hering, Elin Dunevall, Margareta Ek, Gisela Brändén
The rapid growth of antibiotic-resistant bacterial infections is of major concern for human health. Therefore, it is of great importance to characterize novel targets for the development of antibacterial drugs. One promising protein target is MraY (UDP-N-acetylmuramyl-pentapeptide: undecaprenyl phosphate N-acetylmuramyl-pentapeptide-1-phosphate transferase or MurNAc-1-P-transferase), which is essential for bacterial cell wall synthesis. Here, we summarize recent breakthroughs in structural studies of bacterial MraYs and the closely related human GPT (UDP-N-acetylglucosamine: dolichyl phosphate N-acetylglucosamine-1-phosphate transferase or GlcNAc-1-P-transferase)...
May 17, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29775810/a-validated-uplc-ms-ms-method-for-the-quantitation-of-an-unstable-peptide-monocyte-locomotion-inhibitory-factor-mlif-in-human-plasma-and-its-application-to-a-pharmacokinetic-study
#13
Xuemei Liu, Pei Hu, Yongsheng Wang, Xizhu Wang, Jinghua Huang, Jin Li, Cheng Li, Hongyun Wang, Ji Jiang
Monocyte locomotion inhibitory factor (MLIF, Met-Gln-Cys-Asn-Ser), a pentapeptide with anti-inflammatory activity, was developed for neural protection in acute ischemic stroke. Determination of MLIF in human plasma samples is of great importance for pharmacokinetic evaluation in clinical studies. A reliable and sensitive method based on ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) was established for the measurement of MLIF in human plasma. Instability of peptide in matrix was the primary challenge in method development, which was properly resolved by addition of acidification reagents like sulfuric acid...
April 10, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29773503/kakeromamide-a-a-new-cyclic-pentapeptide-inducing-astrocyte-differentiation-isolated-from-the-marine-cyanobacterium-moorea-bouillonii
#14
Fumiaki Nakamura, Hiroshi Maejima, Midori Kawamura, Daisuke Arai, Tatsufumi Okino, Meng Zhao, Tao Ye, Jungyeol Lee, Young-Tae Chang, Nobuhiro Fusetani, Yoichi Nakao
Kakeromamide A (1), a new cyclic pentapeptide encompassing a thiazole ring moiety and a β-amino acid, was isolated from the marine cyanobacterium Moorea bouillonii. Its structure was elucidated by the spectral analysis and the modified Marfey's method. Compound 1 induced differentiation of neural stem cells into astrocytes at the concentration of 10 µM.
April 30, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29767237/a-novel-anti%C3%A2-proliferative-pentapeptide-ilymp-isolated-from-cyclina-sinensis-protein-hydrolysate-induces-apoptosis-of-du%C3%A2-145-prostate-cancer-cells
#15
Fangmiao Yu, Yaru Zhang, Lei Ye, Yunping Tang, Guofang Ding, Xiaojun Zhang, Zuisu Yang
Prostate cancer is the main causes of cancer associated mortality in men worldwide, cancer patients often suffer serious side effects when treated with chemotherapy or radiotherapy, therefore novel drugs are in high demand to treat prostate cancer. In the present study, a pentapeptide (Ile‑Leu‑Tyr‑Met‑Pro; ILYMP) with a molecular weight of 635.71 Da was isolated from the protein hydrolysate of Cyclina sinensis via ultrafiltration and chromatographic methods, and subsequently named Cyclina sinensis pentapeptide (CSP)...
May 14, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29742459/amino-acid-content-of-beta-strands-and-alpha-helices-depends-on-their-flanking-secondary-structure-elements
#16
Vladislav Victorovich Khrustalev, Tatyana Aleksandrovna Khrustaleva, Victor Vitoldovich Poboinev
The influence of flanking structures (alpha helices and beta strands in the primary sequence) on amino acid content of the elements of secondary structure has been analyzed in seven sets of nonhomologous proteins. Elevated usage of beta structural amino acid residues and pentapeptides in beta strands between two alpha helices can be explained by the stabilization of secondary structure of those beta strands by natural selection. High usage of alpha helical amino acids and pentapeptides in beta strands situated between two other beta strands is an evidence of the relaxation of natural selection: "passive" beta strands in these fragments of polypeptide chains are frequently formed due to the influence of flanking "active" beta strands...
May 6, 2018: Bio Systems
https://www.readbyqxmd.com/read/29736598/photodissociative-cross-linking-of-non-covalent-peptide-peptide-ion-complexes-in-the-gas-phase
#17
Huong T H Nguyen, Prokopis C Andrikopoulos, Lubomír Rulíšek, Christopher J Shaffer, František Tureček
We report a gas-phase UV photodissociation study investigating non-covalent interactions between neutral hydrophobic pentapeptides and peptide ions incorporating a diazirine-tagged photoleucine residue. Phenylalanine (Phe) and proline (Pro) were chosen as the conformation-affecting residues that were incorporated into a small library of neutral pentapeptides. Gas-phase ion-molecule complexes of these peptides with photo-labeled pentapeptides were subjected to photodissociation. Selective photocleavage of the diazirine ring at 355 nm formed short-lived carbene intermediates that underwent cross-linking by insertion into H-X bonds of the target peptide...
May 7, 2018: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/29735762/two-dd-carboxypeptidases-from-mycobacterium-smegmatis-affect-cell-surface-properties-through-regulation-of-peptidoglycan-cross-linking-and-glycopeptidolipids
#18
Satya Deo Pandey, Shilpa Pal, Ganesh Kumar N, Ankita Bansal, Sathi Mallick, Anindya S Ghosh
During the peptidoglycan (PG) maturation of mycobacteria, the glycan strands are interlinked by both 3-3 (between two meso-DAP) and 4-3 cross-links (between D-ala and meso-DAP), though there is a predominance (60-80%) of 3-3 cross-links. The DD-CPases act on pentapeptides to generate tetrapeptides that are used by LD-transpeptidases as substrates to form 3-3 cross-links. Therefore, DD-CPases play a crucial role in mycobacterial PG cross-link formation. However, the physiology of DD-CPases in mycobacteria is relatively unexplored...
May 7, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29716322/a-tandem-mass-spectrometer-for-crossed-beam-irradiation-of-mass-selected-molecular-systems-by-kev-atomic-ions
#19
Lucas Schwob, Mathieu Lalande, Jean-Yves Chesnel, Alicja Domaracka, Bernd A Huber, Sylvain Maclot, Jean-Christophe Poully, Jimmy Rangama, Patrick Rousseau, Violaine Vizcaino, Lamri Adoui, Alain Méry
In the present paper, we describe a new home-built crossed-beam apparatus devoted to ion-induced ionization and fragmentation of isolated biologically relevant molecular systems. The biomolecular ions are produced by an electrospray ionization source, mass-over-charge selected, accumulated in a 3D ion trap, and then guided to the extraction region of an orthogonal time-of-flight mass spectrometer. Here, the target molecular ions interact with a keV atomic ion beam produced by an electron cyclotron resonance ion source...
April 2018: Review of Scientific Instruments
https://www.readbyqxmd.com/read/29713626/peptide-modified-zno-nanoparticles-as-gas-sensors-array-for-volatile-organic-compounds-vocs
#20
Marcello Mascini, Sara Gaggiotti, Flavio Della Pelle, Corrado Di Natale, Sinazo Qakala, Emmanuel Iwuoha, Paola Pittia, Dario Compagnone
In this work a peptide based gas sensor array based of ZnO nanoparticles (ZnONPs) has been realized. Four different pentapeptides molecularly modeled for alcohols and esters having cysteine as a common spacer have been immobilized onto ZnONPs. ZnONPs have been morphologically and spectroscopically characterized. Modified nanoparticles have been then deposited onto quartz crystal microbalances (QCMs) and used as gas sensors with nitrogen as carrier gas. Analysis of the pure compounds modeled demonstrated a nice fitting of modeling with real data...
2018: Frontiers in Chemistry
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