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Protein chemistry

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https://www.readbyqxmd.com/read/27913843/molecular-evolution-in-historical-perspective
#1
Edna Suárez-Díaz
In the 1960s, advances in protein chemistry and molecular genetics provided new means for the study of biological evolution. Amino acid sequencing, nucleic acid hybridization, zone gel electrophoresis, and immunochemistry were some of the experimental techniques that brought about new perspectives to the study of the patterns and mechanisms of evolution. New concepts, such as the molecular evolutionary clock, and the discovery of unexpected molecular phenomena, like the presence of repetitive sequences in eukaryotic genomes, eventually led to the realization that evolution might occur at a different pace at the organismic and the molecular levels, and according to different mechanisms...
December 2, 2016: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/27911411/preparation-and-in-vivo-use-of-an-activity-based-probe-for-n-acylethanolamine-acid-amidase
#2
Elisa Romeo, Silvia Pontis, Stefano Ponzano, Fabiola Bonezzi, Marco Migliore, Simona Di Martino, Maria Summa, Daniele Piomelli
Activity-based protein profiling (ABPP) is a method for the identification of an enzyme of interest in a complex proteome through the use of a chemical probe that targets the enzyme's active sites. A reporter tag introduced into the probe allows for the detection of the labeled enzyme by in-gel fluorescence scanning, protein blot, fluorescence microscopy, or liquid chromatography-mass spectrometry. Here, we describe the preparation and use of the compound ARN14686, a click chemistry activity-based probe (CC-ABP) that selectively recognizes the enzyme N-acylethanolamine acid amidase (NAAA)...
November 23, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27904243/a-systematic-approach-to-patients-with-jaundice
#3
REVIEW
Bilal Gondal, Andrew Aronsohn
Jaundice is a clinical manifestation of disorders of underlying bilirubin metabolism, hepatocellular dysfunction, or biliary obstruction. As clinical presentations of yellowing of eyes or skin can be somewhat nonspecific for the underlying etiology of disease, a stepwise approach to evaluation is necessary for accurate diagnosis and effective treatment plan. In this review, we discuss underlying mechanisms of cholestasis and jaundice as well as laboratory and imaging modalities needed to evaluate a patient presenting with hyperbilirubinemia...
December 2016: Seminars in Interventional Radiology
https://www.readbyqxmd.com/read/27896068/metagenomic-investigation-of-the-microbial-diversity-in-a-chrysotile-asbestos-mine-pit-pond-lowell-vermont-usa
#4
Heather E Driscoll, James J Vincent, Erika L English, Elizabeth D Dolci
Here we report on a metagenomics investigation of the microbial diversity in a serpentine-hosted aquatic habitat created by chrysotile asbestos mining activity at the Vermont Asbestos Group (VAG) Mine in northern Vermont, USA. The now-abandoned VAG Mine on Belvidere Mountain in the towns of Eden and Lowell includes three open-pit quarries, a flooded pit, mill buildings, roads, and > 26 million metric tons of eroding mine waste that contribute alkaline mine drainage to the surrounding watershed. Metagenomes and water chemistry originated from aquatic samples taken at three depths (0...
December 2016: Genomics Data
https://www.readbyqxmd.com/read/27891064/proteomic-based-approach-for-characterizing-4-hydroxy-2-nonenal-induced-oxidation-of-buffalo-bubalus-bubalis-and-goat-capra-hircus-meat-myoglobins
#5
Naveena B Maheswarappa, K Usha Rani, Y Praveen Kumar, Vinayak V Kulkarni, Srikanth Rapole
BACKGROUND: Myoglobin (Mb) is a sarcoplasmic heme protein primarily responsible for meat color and its chemistry is species specific. 4-hydroxy-2-nonenal (HNE) is a cytotoxic lipid derived aldehyde detected in meat and was reported to covalently adduct with nucleophilic histidine residues of Mb and predispose it to greater oxidation. However, no literature is available on characterization of lipid oxidation induced oxidation of Indian water buffalo (Bubalus bubalis) and goat (Capra hircus) myoglobins...
2016: Proteome Science
https://www.readbyqxmd.com/read/27890782/bromodomain-histone-readers-and-cancer
#6
REVIEW
Abhinav K Jain, Michelle C Barton
Lysine acetylation of histone proteins is a fundamental post-translational modification that regulates chromatin structure and plays an important role in gene transcription. Aberrant levels of histone lysine acetylation are associated with the development of several diseases. Acetyl-lysine modifications create docking sites for bromodomains, which are structurally conserved modules present in transcription-associated proteins that are termed "reader" proteins. Bromodomain-containing reader proteins are part of multi-protein complexes that regulate transcription programs, often associated with profound phenotypic changes...
November 24, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27889417/dietary-zinc-and-incident-calcium-kidney-stones-in-adolescence
#7
Gregory E Tasian, Michelle E Ross, Lihai Song, Robert W Grundmeier, James Massey, Michelle R Denburg, Lawrence Copelovitch, Steven Warner, Thomas Chi, David W Killilea, Marshall L Stoller, Susan L Furth
PURPOSE: To determine the association between dietary zinc intake and incident calcium kidney stones and examine the relationship between dietary zinc intake and urinary zinc excretion among adolescents. MATERIAL AND METHODS: This study was a nested case-control study conducted within a large pediatric healthcare system. Three 24-hour dietary recalls and spot urine chemistries were obtained for 30 participants aged 12-18 years with a first idiopathic calcium-based kidney stone and 30 healthy controls, matched on age, sex, race, and month of enrollment...
November 23, 2016: Journal of Urology
https://www.readbyqxmd.com/read/27889088/osteoblast-cellular-activity-on-low-elastic-modulus-ti-24nb-4zr-8sn-alloy
#8
K C Nune, R D K Misra, S J Li, Y L Hao, R Yang
OBJECTIVES: Low modulus β-titanium alloys with non-toxic alloying elements are envisaged to provide good biocompatibility and alleviate the undesired stress shielding effect. The objective of this study is to fundamentally elucidate the biological response of novel high strength-low elastic modulus Ti2448 alloy through the study of bioactivity and osteoblast cell functions. METHODS: Characterization techniques such as SEM, EDX, XRD, and fluorescence microscopy were utilized to analyze the microstructure, morphology, chemical composition, and cell adhesion...
November 23, 2016: Dental Materials: Official Publication of the Academy of Dental Materials
https://www.readbyqxmd.com/read/27885781/cellular-response-of-osteoblasts-to-low-modulus-ti-24nb-4zr-8sn-alloy-mesh-structure
#9
K C Nune, R D K Misra, S J Li, Y L Hao, R Yang
Titanium alloys (Ti-6Al-4V and Ti-6Al-7Nb) are widely used for implants, which are characterized by high elastic modulus (∼110 GPa) with (α + β) structure and that may induce undesirable stress shielding effect and immune responses associated with the presence of toxic elements. In this regard, we have combined the attributes of a new alloy design and the concept of additive manufacturing to fabricate 3D scaffolds with an interconnected porous structure. The new alloy is a β-type Ti-24Nb-4Zr-8Sn (Ti2448) alloy with significantly reduced modulus...
November 25, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27885032/directed-evolution-of-cytochrome-c-for-carbon-silicon-bond-formation-bringing-silicon-to-life
#10
S B Jennifer Kan, Russell D Lewis, Kai Chen, Frances H Arnold
Enzymes that catalyze carbon-silicon bond formation are unknown in nature, despite the natural abundance of both elements. Such enzymes would expand the catalytic repertoire of biology, enabling living systems to access chemical space previously only open to synthetic chemistry. We have discovered that heme proteins catalyze the formation of organosilicon compounds under physiological conditions via carbene insertion into silicon-hydrogen bonds. The reaction proceeds both in vitro and in vivo, accommodating a broad range of substrates with high chemo- and enantioselectivity...
November 25, 2016: Science
https://www.readbyqxmd.com/read/27884192/role-of-cytochrome-c-in-%C3%AE-synuclein-radical-formation-implications-of-%C3%AE-synuclein-in-neuronal-death-in-maneb-and-paraquat-induced-model-of-parkinson-s-disease
#11
Ashutosh Kumar, Douglas Ganini, Ronald P Mason
BACKGROUND: The pathological features of Parkinson's disease (PD) include an abnormal accumulation of α-synuclein in the surviving dopaminergic neurons. Though PD is multifactorial, several epidemiological reports show an increased incidence of PD with co-exposure to pesticides such as Maneb and paraquat (MP). In pesticide-related PD, mitochondrial dysfunction and α-synuclein oligomers have been strongly implicated, but the link between the two has not yet been understood. Similarly, the biological effects of α-synuclein or its radical chemistry in PD is largely unknown...
November 24, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27883932/biological-response-of-human-suture-mesenchymal-cells-to-titania-nanotube-based-implants-for-advanced-craniosynostosis-therapy
#12
Manpreet Bariana, Prem Dwivedi, Sarbin Ranjitkar, John A Kaidonis, Dusan Losic, Peter J Anderson
Titania nanotubes (TNTs) engineered on titanium (Ti) surfaces (i.e. TNT/Ti) and loaded with specific drugs have been recognised as a promising solution for localised therapeutic delivery to address several medical problems not feasible with conventional drug administration. We propose the use of TNT/Ti protein-releasing implants to treat paediatric craniofacial abnormality in craniosynostosis caused by premature fusion of cranial sutures. In this study, we have analysed the biological response of human suture mesenchymal cells (SMCs), extracted from two different patients undergoing craniofacial reconstruction surgery, at the TNT/Ti implant surface...
November 17, 2016: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/27878643/the-evolution-of-drug-design-at-merck-research-laboratories
#13
Frank K Brown, Edward C Sherer, Scott A Johnson, M Katharine Holloway, Bradley S Sherborne
On October 5, 1981, Fortune magazine published a cover article entitled the "Next Industrial Revolution: Designing Drugs by Computer at Merck". With a 40+ year investment, we have been in the drug design business longer than most. During its history, the Merck drug design group has had several names, but it has always been in the "design" business, with the ultimate goal to provide an actionable hypothesis that could be tested experimentally. Often the result was a small molecule but it could just as easily be a peptide, biologic, predictive model, reaction, process, etc...
November 23, 2016: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/27876144/in-tip-nanoreactors-for-cancer-cells-proteome-profiling
#14
Ling Yan, Liang Qiao, Ji Ji, Yixin Li, Xuefei Yin, Ling Lin, Xiaohui Liu, Jun Yao, Yi Wang, Bin Liu, Kun Qian, Baohong Liu, Pengyuan Yang
Mass spectrometry (MS)-based proteome profiling is essential for molecular diagnostics in modern biomedical study. To date, sample preparation including protein extraction and proteolysis is still very challenging and lack of efficiency. Recently tips-based sample preparation protocols exhibit strong potentials to achieve the goal of "a proteome in an hour". However, in-tip proteolysis is still rarely reported and far from ideal for dealing with complex bio-samples. In this work, nanoreactors encapsulated micropipette tips were demonstrated as high performance devices for fast (∼minutes) and multiplexing proteolysis to assist the profiling of cancer cells proteome...
January 1, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/27875310/extending-halogen-based-medicinal-chemistry-to-proteins-iodo-insulin-as-a-case-study
#15
Krystel El Hage, Vijay Pandyarajan, Nelson B Phillips, Brian J Smith, John G Menting, Jonathan Whittaker, Michael C Lawrence, Markus Meuwly, Michael A Weiss
Insulin, a protein critical for metabolic homeostasis, provides a classical model for protein design with application to human health. Recent efforts to improve its pharmaceutical formulation demonstrated that iodination of a conserved tyrosine (Tyr(B26)) enhances key properties of a rapid-acting clinical analog. Moreover, the broad utility of halogens in medicinal chemistry has motivated use of hybrid quantum- and molecular-mechanical methods to study proteins. Here, we (i) undertook quantitative atomic-level simulations of 3-I-Tyr(B26)-insulin to predict its structural features and (ii) tested these predictions by X-ray crystallography...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27874966/from-additivity-to-cooperativity-in-chemistry-can-cooperativity-be-measured
#16
Armido Studer, Ludger Tebben, Christian Mück-Lichtenfeld, Gustavo Fernández, Stefan Grimme
Cooperative effects can be observed in various research areas in chemistry. Cooperative catalysis is meanwhile well established, assembly of compounds on surfaces can be steered by cooperative effects and supramolecular polymerization can proceed in a cooperative fashion. In biological systems, cooperativity is observed in protein-protein-, protein-lipid- and protein-molecule-interactions. Synergistic effects are relevant in frustrated Lewis pairs, organic multispin systems, multimetallic clusters and also in nanoparticles...
November 22, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27874285/modern-tools-for-the-chemical-ligation-and-synthesis-of-modified-peptides-and-proteins
#17
Luca Gentilucci, Pierluigi Tosi, Adriano Bauer, Rossella De Marco
The ability to improve nature's capacity by introducing modification of biological interest in proteins and peptides (P&P) is one of the modern challenges in synthetic chemistry. Due to the unfavorable pharmacokinetic properties, many native P&P are of little use as therapeutic agents. Today, few methods for the preparation of modified proteins are available. Initially introduced to realize the ligation between two standard peptidic sequences, and hence to afford native proteins, the modern chemical methodologies, in other words native chemical ligation, expressed ligation, Staudinger ligation, auxiliary mediated ligation, aldehyde capture, etc...
November 22, 2016: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/27873200/clickable-polymeric-coating-for-glycan-microarrays
#18
Caterina Zilio, Laura Sola, Marina Cretich, Anna Bernardi, Marcella Chiari
The interaction of carbohydrates with a variety of biological targets, including antibodies, proteins, viruses, and cells are of utmost importance in many aspects of biology. Glycan microarrays are increasingly used to determine the binding specificity of glycan-binding proteins. In this study, a novel microarray support is reported for the fabrication of glycan arrays that combines the higher sensitivity of a layered Si-SiO2 surface with a novel polymeric coating easily modifiable by subsequent click reaction...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27873087/key-questions-for-translation-of-ffa-receptors-from-pharmacology-to-medicines
#19
Arthur T Suckow, Celia P Briscoe
The identification of fatty acids as ligands for the G-protein coupled free fatty acid (FFA) receptor family over 10 years ago led to intensive chemistry efforts to find small-molecule ligands for this class of receptors. Identification of potent, selective modulators of the FFA receptors and their utility in medicine has proven challenging, in part due to their complex pharmacology. Nevertheless, ligands have been identified that are sufficient for exploring the therapeutic potential of this class of receptors in rodents and, in the case of FFA1, FFA2, FFA4, and GPR84, also in humans...
November 22, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27872308/atomistic-insight-into-lipid-translocation-by-a-tmem16-scramblase
#20
Neville P Bethel, Michael Grabe
The transmembrane protein 16 (TMEM16) family of membrane proteins includes both lipid scramblases and ion channels involved in olfaction, nociception, and blood coagulation. The crystal structure of the fungal Nectria haematococca TMEM16 (nhTMEM16) scramblase suggested a putative mechanism of lipid transport, whereby polar and charged lipid headgroups move through the low-dielectric environment of the membrane by traversing a hydrophilic groove on the membrane-spanning surface of the protein. Here, we use computational methods to explore the membrane-protein interactions involved in lipid scrambling...
November 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
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