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https://www.readbyqxmd.com/read/28096133/regulation-of-the-iron-homeostatic-hormone-hepcidin
#1
REVIEW
Veena Sangkhae, Elizabeta Nemeth
Iron is required for many biological processes but is also toxic in excess; thus, body iron balance is maintained through sophisticated regulatory mechanisms. The lack of a regulated iron excretory mechanism means that body iron balance is controlled at the level of absorption from the diet. Iron absorption is regulated by the hepatic peptide hormone hepcidin. Hepcidin also controls iron release from cells that recycle or store iron, thus regulating plasma iron concentrations. Hepcidin exerts its effects through its receptor, the cellular iron exporter ferroportin...
January 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28094944/solvent-directed-switch-of-a-left-handed-10-12-helix-into-a-right-handed-12-10-helix-in-mixed-beta-peptides
#2
Prashanth Thodupunuri, Sirisha Katukuri, Kallaganti V S Ramakrishna, Gangavaram V M Sharma, Ajit C Kunwar, Akella V S Sarma, Hans-Jörg Hofmann
Present study describes the synthesis and conformational analysis of β-peptides from C-linked carbo-β-amino acids [β-Caa(l)] with a D-lyxo furanoside side chain and β-hGly in 1:1 alternation. NMR and CD investigations on peptides with an (S)-β-Caa(l) monomer at the N-terminus revealed a right-handed 10/12-mixed helix. An unprecedented solvent-directed 'switch' both in helical pattern and handedness was observed when the sequence begins with a β-hGly residue instead of a (S)-β-Caa(l) constituent. NMR studies on these peptides in chloroform indicated a left-handed 10/12-helix, while the CD spectrum in methanol inferred a right-handed secondary structure...
January 17, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28094875/neuroendocrinology-of-mast-cells-challenges-and-controversies
#3
REVIEW
Theoharis C Theoharides
Mast cells (MC) are hemopoietically-derived tissue immune cells that are ubiquitous in the body, including neuroendocrine organs such as the hypothalamus, pineal, pituitary, ovaries, pancreas and uterus where their action is not well understood. Mast cells have historically been associated with allergies because of their rich content of histamine and tryptase, but more recently with regulation of immunity and inflammation due their synthesis and release of numerous cytokines and chemokines. Mast cells are located perivascularly and express numerous receptors for diverse ligands such as allergens, pathogens, neurotransmitters, neuropeptides and hormones including acetylcholine, calcitonin gene-related peptide (CGRP), corticosteroids, corticotropin-releasing hormone (CRH), β-endorphin, epinephrine, 17β-estradiol, gonadotrophins, hemokinin-A (HKA), leptin, melatonin, neurotensin (NT), parathyroid hormone (PTH), substance P (SP) and vasoactive instestinal peptide (VIP)...
January 17, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28093469/assembly-of-the%C3%A2-elongated-collagen-prolyl-4-hydroxylase-%C3%AE-2%C3%AE-2-heterotetramer%C3%A2-around-a-central-%C3%AE-2-dimer
#4
Kristian Koski, Jothi Anantharajan, Petri Kursula, Prathusha Dhavala, Abhinandan Venkatesha Murthy, Ulrich Bergmann, Johanna Myllyharju, Rik K Wierenga
COLLAGEN PROLYL 4-HYDROXYLASE C-P4H, AN Α2Β2 HETEROTETRAMER, IS A CRUCIAL ENZYME FOR COLLAGEN SYNTHESIS THE Α SUBUNIT CONSISTS OF AN N TERMINAL DIMERIZATION DOMAIN, A CENTRAL PEPTIDE-SUBSTRATE-BINDING PSB DOMAIN, AND A C TERMINAL CATALYTIC CAT DOMAIN THE Β SUBUNIT ALSO KNOWN AS PROTEIN DISULFIDE ISOMERASE PDI ACTS AS A CHAPERONE, STABILIZING THE FUNCTIONAL CONFORMATION OF C-P4H C-P4H HAS BEEN STUDIED FOR DECADES, BUT ITS STRUCTURE HAS REMAINED ELUSIVE HERE, WE PRESENT : A THREE-DIMENSIONAL SMALL-ANGLE X-RAY SCATTERING SAXS MODEL OF THE ENTIRE HUMAN C-P4H-I HETEROTETRAMER C-P4H IS AN ELONGATED, BILOBAL, SYMMETRIC MOLECULE WITH A LENGTH OF 290 Å THE DIMERIZATION DOMAINS FROM THE TWO A SUBUNITS FORM A PROTEIN-PROTEIN DIMER INTERFACE, ASSEMBLED AROUND THE CENTRAL ANTIPARALLEL COILED-COIL INTERFACE OF THEIR N TERMINAL Α HELICES THIS REGION FORMS A THIN WAIST IN THE BILOBAL TETRAMER THE TWO PSB/CAT UNITS, EACH COMPLEXED WITH A PDI/Β SUBUNIT, FORM TWO BULKY LOBES POINTING OUTWARD FROM THIS WAIST REGION, SUCH THAT THE PDI/Β SUBUNITS LOCATE AT THE FAR ENDS OF THE ΒΑΑΒ COMPLEX THE PDI/Β SUBUNIT INTERACTS EXTENSIVELY WITH THE CAT DOMAIN THE ASYMMETRIC SHAPE OF TWO TRUNCATED C-P4H-I VARIANTS, ALSO CHARACTERIZED IN THIS STUDY, AGREES WITH THIS ASSEMBLY FURTHERMORE, DATA FROM THESE TRUNCATED VARIANTS SHOW THAT DIMERIZATION BETWEEN THE A SUBUNITS HAS AN IMPORTANT ROLE IN ACHIEVING THE CORRECT PSB-CAT ASSEMBLY COMPETENT FOR CATALYTIC ACTIVITY KINETIC ASSAYS WITH VARIOUS PROLINE-RICH PEPTIDE SUBSTRATES AND INHIBITORS SUGGEST THAT IN THE COMPETENT ASSEMBLY, THE PSB DOMAIN BINDS TO THE PROCOLLAGEN SUBSTRATE DOWNSTREAM FROM THE CAT DOMAIN...
January 16, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28093409/deuterater-a-tool-for-quantifying-peptide-isotope-precision-and-kinetic-proteomics
#5
Bradley C Naylor, Michael T Porter, Elise Wilson, Adam Herring, Spencer Lofthouse, Austin Hannemann, Stephen R Piccolo, Alan L Rockwood, John C Price
MOTIVATION: Using mass spectrometry to measure the concentration and turnover of the individual proteins in a proteome, enables the calculation of individual synthesis and degradation rates for each protein. Software to analyze concentration is readily available, but software to analyze turnover is lacking. Data analysis workflows typically don't access the full breadth of information about instrument precision and accuracy that is present in each peptide isotopic envelope measurement...
January 16, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28093123/synthesis-of-stable-isotopically-labeled-peptides-with-filter-assisted-enzymatic-labeling-for-the-diagnosis-of-hepatitis-b-virus-infection-utilizing-mass-spectrometry-based-proteomics-strategy
#6
Hsing-Fen Tsai, He-Hsuan Hsiao
A facile method for the preparation of stable isotopically labeled peptides was developed by means of filter-assisted tryptic (16)O/(18)O water labeling, which could be directly applied to the determination of hepatitis B virus infection from human serum with tandem mass spectrometry. Tryptic peptides of hepatitis B surface antigen or hepatitis B e antigen from different subtypes of hepatitis B virus were synthesized with traditional solid-phase peptide synthesis as potential biomarkers. Trypsin catalyzed oxygen-18 exchange at their amidated c-terminus of arginine or lysine residue...
March 1, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28092044/high-throughput-quantification-of-sh2-domain-phosphopeptide-interactions-with-cellulose-peptide-conjugate-microarrays
#7
Brett W Engelmann
The Src Homology 2 (SH2) domain family primarily recognizes phosphorylated tyrosine (pY) containing peptide motifs. The relative affinity preferences among competing SH2 domains for phosphopeptide ligands define "specificity space," and underpins many functional pY mediated interactions within signaling networks. The degree of promiscuity exhibited and the dynamic range of affinities supported by individual domains or phosphopeptides is best resolved by a carefully executed and controlled quantitative high-throughput experiment...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28091894/mechanisms-of-action-of-surgical-interventions-on-weight-related-diseases-the-potential-role-of-bile-acids
#8
REVIEW
Mohsen Mazidi, Pedro Paulo P de Caravatto, John R Speakman, Ricardo V Cohen
Surgical interventions for weight-related diseases (SWRD) may have substantial and sustainable effect on weight reduction, also leading to a higher remission rate of type 2 diabetes (T2D) mellitus than any other medical treatment or lifestyle intervention. The resolution of T2D after Roux-en-Y gastric bypass (RYGB) typically occurs too quickly to be accounted for by weight loss alone, suggesting that these operations have a direct impact on glucose homeostasis. The mechanisms underlying these beneficial effects however remain unclear...
January 14, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28091672/a-rapid-way-to-discover-nonstandard-macrocyclic-peptide-modulators-of-drug-targets
#9
Toby Passioura, Hiroaki Suga
Studies of the fundamental nature of RNA catalysis and the potential mechanism of a shift from the "RNA world" to proteinaceous life lead us to identify a set of ribozymes (flexizymes) capable of promiscuous tRNA acylation. Whilst theoretically and mechanistically interesting in their own right, flexizymes have turned out to have immense practical value for the simple synthesis of tRNAs acylated with unusual amino acids, which in turn can be used for the ribosomal synthesis of peptides containing non-canonical residues...
January 16, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28091549/urinary-proteomics-can-define-distinct-diagnostic-inflammatory-arthritis-subgroups
#10
Stefan Siebert, Duncan Porter, Caron Paterson, Rosie Hampson, Daniel Gaya, Agnieszka Latosinska, Harald Mischak, Joost Schanstra, William Mullen, Iain McInnes
Current diagnostic tests applied to inflammatory arthritis lack the necessary specificity to appropriately categorise patients. There is a need for novel approaches to classify patients with these conditions. Herein we explored whether urinary proteomic biomarkers specific for different forms of arthritis (rheumatoid arthritis (RA), psoriatic arthritis (PsA), osteoarthritis (OA)) or chronic inflammatory conditions (inflammatory bowel disease (IBD)) can be identified. Fifty subjects per group with RA, PsA, OA or IBD and 50 healthy controls were included in the study...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090719/diversity-oriented-synthesis-of-cyclic-azapeptides-by-a-3-macrocyclization-provides-high-affinity-cd36-modulating-peptidomimetics
#11
Jinqiang Zhang, Mukandila Mulumba, Huy Ong, William D Lubell
Macrocyclization has enabled the use of peptides in drug discovery creating a need for methods to synthesize diverse peptide macrocycles. Azapeptides have advanced to clinically used drugs, however, few cyclic azapeptides have been studied. A multiple component "A(3) -macrocyclization" strategy is described for the preparation of diverse cyclic azapeptides and is demonstrated by the synthesis of 15 growth hormone releasing hormone-6 (GHRP-6) analogs. Certain cyclic aza-GHRP-6 analogs exhibited unprecedented affinity for the CD36 receptor, and capacity to modulate Toll-like receptor agonist-induced overproduction of nitric oxide, and reduce pro-inflammatory cytokine and chemokine production in macrophages...
January 16, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28090689/%C3%AE-aminoxy-peptoids-a-unique-peptoid-backbone-with-a-preference-for-cis-amide-bonds
#12
Viktoria Krieger, Emanuele Ciglia, Roland Thoma, Vera Vasylyeva, Benedikt Frieg, Nader de Sousa Amadeu, Thomas Kurz, Christoph Janiak, Holger Gohlke, Finn Kristian Hansen
α-Peptoids, or N-substituted glycine oligomers, are an important class of peptidomimetic foldamers with proteolytic stability. Nevertheless, the presence of cis-/trans-amide bond conformers, which contribute to the high flexibility of α-peptoids, is considered as a major drawback. A modified peptoid backbone with an improved control of the amide bond geometry could therefore help to overcome this limitation. Here we have performed the first thorough analysis of the folding propensities of α-aminoxy peptoids (or N-substituted 2-aminoxyacetic acid oligomers)...
January 16, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28090285/pulmonary-vascular-and-ventricular-dysfunction-in-the-susceptible-patient-2015-grover-conference-series
#13
REVIEW
Bradley A Maron, Roberto F Machado, Larissa Shimoda
Pulmonary blood vessel structure and tone are maintained by a complex interplay between endogenous vasoactive factors and oxygen-sensing intermediaries. Under physiological conditions, these signaling networks function as an adaptive interface between the pulmonary circulation and environmental or acquired perturbations to preserve oxygenation and maintain systemic delivery of oxygen-rich hemoglobin. Chronic exposure to hypoxia, however, triggers a range of pathogenetic mechanisms that include hypoxia-inducible factor 1α (HIF-1α)-dependent upregulation of the vasoconstrictor peptide endothelin 1 in pulmonary endothelial cells...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28089773/mitochondrial-diseases-yeast-as-a-model-for-the-study-of-suppressors
#14
Silvia Francisci, Arianna Montanari
Mitochondrial (mt) tRNA gene mutations are an important cause of human morbidity and are associated with different syndromes. We have previously shown that the mitochondrial protein synthesis elongation factor EF-Tu and isolated sequences from the carboxy-terminal domain of yeast and human mt leucyl-tRNA synthetases (LeuRS), have a wide range of suppression capability among different yeast mt tRNA mutants having defective respiratory phenotype. Here we show that the rescuing capability can be restricted to a specific sequence of six amino acids from the carboxy-terminal domain of mt LeuRS...
January 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088445/synthesis-and-exploration-of-novel-radiolabeled-bombesin-peptides-for-targeting-receptor-positive-tumor
#15
Kakali De, Indranil Banerjee, Samarendu Sinha, Shantanu Ganguly
Increasing evidence of peptide receptor overexpression in various cancer cells, warrant the development of receptor specific radiolabeled peptides for molecular imaging and therapy in nuclear medicine. Gastrin-releasing-peptide (GRP) receptor, are overexpressed in a variety of human cancer cells. The present study report the synthesis and biological evaluation of new bombesin (BBN) analogs, HYNIC-Asp-[Phe(13)]BBN(7-13)-NH-CH2-CH2-CH3:BA1, HYNIC-Pro-[Tyr(13)Met(14)]BBN(7-14)NH2:BA2 as prospective tumor imaging agent with compare to BBN(7-14)NH2:BS as standard...
January 11, 2017: Peptides
https://www.readbyqxmd.com/read/28088101/sequenced-defined-biomolecules-for-nanomaterial-synthesis-functionalization-and-assembly
#16
REVIEW
Joseph M Slocik, Rajesh R Naik
Biomolecules represent an invaluable resource to nanotechnology by providing a large diversity of highly functional biomolecular templates. As a result, these have been extensively used for controlling the synthesis, functionalization, and assembly of nanomaterials, while also creating materials with new properties and structures. In the following, we focus on the use of peptides to achieve these goals and describe their general utility, sequence programmability, and use as templates. Also, we highlight several recent advances in the identification and selection of high affinity nanomaterial-binding peptides, provide a few examples of peptide functionalized surfaces and peptide templated materials, and describe how simple modifications to well characterized nanomaterial-binding peptides can be used to manipulate interactions and physiochemical properties...
January 11, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28087353/thiolated-polymers-as-mucoadhesive-drug-delivery-systems
#17
REVIEW
Sarah Duggan, Wayne Cummins, Orla O' Donovan, Helen Hughes, Eleanor Owens
Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug...
January 10, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28078813/host-defense-peptide-derived-privileged-scaffolds-for-anti-infective-drug-discovery
#18
Ersilia Nigro, Irene Colavita, Daniela Sarnataro, Olga Scudiero, Aurora Daniele, Francesco Salvatore, Antonello Pessi
'Privileged scaffolds' are molecular frameworks which have been successfully exploited for small molecule drug discovery. Peptide privileged scaffolds, featuring a strictly conserved multiple-disulfide framework and high variability in the rest of the sequence, display a broad range of biological effects, including antimicrobial and antiviral activity. Unlike small molecules, however, the cost of manufacturing these peptides is high, and their synthesis challenging. We previously described a simplified privileged scaffold corresponding to the γ-core of human β-defensin-3 (HBD3)...
January 12, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28077875/structural-basis-of-co-translational-quality-control-by-arfa-and-rf2-bound-to-ribosome
#19
Fuxing Zeng, Yanbo Chen, Jonathan Remis, Mrinal Shekhar, James C Phillips, Emad Tajkhorshid, Hong Jin
Quality control mechanisms intervene appropriately when defective translation events occur, in order to preserve the integrity of protein synthesis. Rescue of ribosomes translating on messenger RNAs that lack stop codons is one of the co-translational quality control pathways. In many bacteria, ArfA recognizes stalled ribosomes and recruits the release factor RF2, which catalyses the termination of protein synthesis. Although an induced-fit mechanism of nonstop mRNA surveillance mediated by ArfA and RF2 has been reported, the molecular interaction between ArfA and RF2 in the ribosome that is responsible for the mechanism is unknown...
January 11, 2017: Nature
https://www.readbyqxmd.com/read/28077628/the-creatininase-homolog-mfte-from-mycobacterium-smegmatis-catalyzes-a-peptide-cleavage-reaction-in-the-biosynthesis-of-a-novel-ripp
#20
Nathan A Bruender, Vahe Bandarian
Most ribosomally-synthesized and post-translationally modified peptide (RiPP) natural products are processed by tailoring enzymes to create complex natural products that are still recognizably peptide-based. However, some tailoring enzymes dismantle the peptide en route to synthesis of small molecules. The biosynthesis of a small-molecule natural product of as yet unknown structure, mycofactocin, is thought to be synthesized in this way, via the mft gene cluster found in many strains of Mycobacteria. This cluster harbors at least six genes, which appear to be conserved across species...
January 11, 2017: Journal of Biological Chemistry
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