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Javier Garcia-Pardo, Sebastian Tanco, Lucía Díaz, Sayani Dasgupta, Juan Fernandez-Recio, Julia Lorenzo, Francesc X Aviles, Lloyd D Fricker
Metallocarboxypeptidase D (CPD) is a membrane-bound component of the trans-Golgi network that cycles to the cell surface through exocytic and endocytic pathways. Unlike other members of the metallocarboxypeptidase family, CPD is a multicatalytic enzyme with three carboxypeptidase-like domains, although only the first two domains are predicted to be enzymatically active. To investigate the enzymatic properties of each domain in human CPD, a critical active site Glu in domain I and/or II was mutated to Gln and the protein expressed, purified, and assayed with a wide variety of peptide substrates...
2017: PloS One
Magdalena Krochmal, Georgia Kontostathi, Pedro Magalhães, Manousos Makridakis, Julie Klein, Holger Husi, Johannes Leierer, Gert Mayer, Jean-Loup Bascands, Colette Denis, Jerome Zoidakis, Petra Zürbig, Christian Delles, Joost P Schanstra, Harald Mischak, Antonia Vlahou
Mechanisms underlying the onset and progression of nephropathy in diabetic patients are not fully elucidated. Deregulation of proteolytic systems is a known path leading to disease manifestation, therefore we hypothesized that proteases aberrantly expressed in diabetic nephropathy (DN) may be involved in the generation of DN-associated peptides in urine. We compared urinary peptide profiles of DN patients (macroalbuminuric, n = 121) to diabetic patients with no evidence of DN (normoalbuminuric, n = 118)...
November 9, 2017: Scientific Reports
Matteo Bosso, Ludger Ständker, Frank Kirchhoff, Jan Münch
Infectious diseases and cancers are leading causes of death and pose major challenges to public health. The human peptidome encompasses millions of compounds that display an enormous structural and functional diversity and represents an excellent source for the discovery of endogenous agents with antimicrobial and/or anticancer activity. Here, we discuss how to exploit the human peptidome for novel antimicrobial and anticancer agents through the generation of peptide libraries from human body fluids and tissues and stepwise purification of bioactive compounds...
October 31, 2017: Bioorganic & Medicinal Chemistry
Baptiste Houyvet, Yolande Bouchon-Navaro, Claude Bouchon, Didier Goux, Benoît Bernay, Erwan Corre, Céline Zatylny-Gaudin
The present study characterizes for the first time an antimicrobial peptide in lionfish (Pterois volitans), a venomous fish. Using a peptidomic approach, we identified a mature piscidin in lionfish and called it pteroicidin-α. We detected an amidated form (pteroicidin-α- CONH2) and a non-amidated form (pteroicidin-α-COOH), and then performed their functional and structural study. Interestingly, the two peptides displayed different antibacterial and hemolytic activity levels. Pteroicidin-α-CONH2 was bactericidal on human pathogens like Staphylococcus aureus or Escherichia coli, as well as on the fish pathogen Aeromonas salmonicida, while pteroicidin-α-COOH only inhibited their growth...
November 11, 2017: Fish & Shellfish Immunology
Rachel Marty, Saghar Kaabinejadian, David Rossell, Michael J Slifker, Joris van de Haar, Hatice Billur Engin, Nicola de Prisco, Trey Ideker, William H Hildebrand, Joan Font-Burgada, Hannah Carter
MHC-I molecules expose the intracellular protein content on the cell surface, allowing T cells to detect foreign or mutated peptides. The combination of six MHC-I alleles each individual carries defines the sub-peptidome that can be effectively presented. We applied this concept to human cancer, hypothesizing that oncogenic mutations could arise in gaps in personal MHC-I presentation. To validate this hypothesis, we developed and applied a residue-centric patient presentation score to 9,176 cancer patients across 1,018 recurrent oncogenic mutations...
October 20, 2017: Cell
Markus Müller, David Gfeller, George Coukos, Michal Bassani-Sternberg
The remarkable clinical efficacy of the immune checkpoint blockade therapies has motivated researchers to discover immunogenic epitopes and exploit them for personalized vaccines. Human leukocyte antigen (HLA)-binding peptides derived from processing and presentation of mutated proteins are one of the leading targets for T-cell recognition of cancer cells. Currently, most studies attempt to identify neoantigens based on predicted affinity to HLA molecules, but the performance of such prediction algorithms is rather poor for rare HLA class I alleles and for HLA class II...
2017: Frontiers in Immunology
Ning Yang, Krishna D B Anapindi, Elena V Romanova, Stanislav S Rubakhin, Jonathan V Sweedler
Measurement, identification, and quantitation of endogenous peptides in tissue samples by mass spectrometry (MS) contribute to our understanding of the complex molecular mechanisms of numerous biological phenomena. For accurate results, it is essential to arrest the postmortem degradation of ubiquitous proteins in samples prior to performing peptidomic measurements. Doing so ensures that the detection of endogenous peptides, typically present at relatively low levels of abundance, is not overwhelmed by protein degradation products...
November 3, 2017: Analyst
Gilda Aiello, Carmen Lammi, Giovanna Boschin, Chiara Zanoni, Anna Arnoldi
The seed of industrial hemp is an underexploited protein source. In view of a possible use in functional foods, a hempseed protein concentrate was hydrolyzed with pepsin, trypsin, pancreatin, or a mixture of these enzymes. A detailed peptidomic analysis using data-dependent acquisition showed that the numbers of peptides identified ranged from 90 belonging to 33 parent proteins in the peptic hydrolysate to 9 belonging to 6 proteins in the pancreatin digest. The peptic and tryptic hydrolysates resulted to be the most efficient inhibitors of 3-hydroxymethyl-coenzyme A reductase activity, when tested on the catalytic domain of the enzyme...
November 2, 2017: Journal of Agricultural and Food Chemistry
V A Sergeeva, K T Muminova, N L Starodubtseva, A S Kononikhin, A E Bugrova, M I Indeykina, V V Baibakova, Z S Khodzhaeva, N E Kan, V E Frankevich, R G Shmakov, E N Nikolaev, G T Sukhikh
In order to find a peptide panel to differentiate close hypertensive conditions a case-control study was designed for 64 women from 4 groups: preeclampsia (PE), chronic hypertension superimposed with PE, chronic hypertension, and healthy individuals. Chromatography coupled with mass-spectrometry and subsequent bioinformatic analysis showed several patterns in the changes of the urine peptidome. There were 36 peptides common for four groups. Twenty two of them 22 belonged to alpha-1-chain of collagen I, nine peptides were from alpha-1-chain of collagen III, two from alpha-2-chain of collagen I, one from alpha-1/2-chain of collagen I, one from alpha-1-chain of collagen I/XVIII and one from uromodulin...
October 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
Neha Patel, Nadiatul A Mohd-Radzman, Leo Corcilius, Ben Crossett, Angela Connolly, Stuart J Cordwell, Ariel Ivanovici, Katia Taylor, James Wlilliams, Steve Binos, Michael Mariani, Richard J Payne, Michael A Djordjevic
Multigene families encoding diverse secreted peptide hormones play important roles in plant development. A need exists to efficiently elucidate the structures and post-translational modifications of these difficult-to-isolate peptide hormones in planta so that their biological functions can be determined. A mass spectrometry and bioinformatics approach was developed to comprehensively analyse the secreted peptidome of Medicago hairy root cultures and xylem sap. We identified 759 spectra corresponding to the secreted products of twelve peptide hormones including four CEP (C-TERMINALLY ENCODED PEPTIDE), two CLE (CLV3/ENDOSPERM SURROUNDING REGION RELATED) and six XAP (XYLEM SAP ASSOCIATED PEPTIDE) peptides...
October 27, 2017: Molecular & Cellular Proteomics: MCP
Yan-Ping Wu, Jie Deng, Shu-Hua Ouyang, Zhong-Fu Mao, Guo-En Wang, Hiroshi Kurihara, Rong-Rong He, Yi-Fang Li
Polypeptides extracted from animal immune organs have been proved to exert immunomodulatory activities in previous reports. However, relative experimental data regarding the influence of a polypeptide mixture extracted from healthy calf spleen (lienal polypeptide [LP]) on the immune function in tumor therapy are limited, and the components in LP remain unclear. In the present study, the immune regulatory effect of LP was investigated in normal mice and Lewis lung carcinoma (LLC)-bearing mice treated with cyclophosphamide (CTX)...
January 1, 2017: Experimental Biology and Medicine
Alberto Tonda, Anita Grosvenor, Stefan Clerens, Steven Le Feunteun
This paper presents a novel model of protein hydrolysis and release of peptides by endoproteases. It requires the amino-acid sequence of the protein substrate to run, and makes use of simple Monte-Carlo in silico simulations to qualitatively and quantitatively predict the peptides that are likely to be produced during the course of the proteolytic reaction. In the present study, the model is applied to the case of pepsin, the gastric protease. Unlike pancreatic proteases, pepsin has a low substrate specificity and therefore displays a stochastic behavior that is particularly challenging to model and predict...
October 26, 2017: Food & Function
Yun Yang, Ju Bai, Wei Li, Ai-Li He, Jian-Li Wang, Fang-Xia Wang
OBJECTIVE: To screen serum peptide associated with renal impairment in patients with multiple myeloma(MM) and search early biomarker of MM renal impairment. METHODS: The weak cation exchange magnetic bead combined with matrix assisted laser desorption/ionization time of flight mass spectrometry was used to compare and analyze serum peptidome of MM with or without renal impairment. RESULTS: There were 18 peptide peaks with statistical significance in the molecular weight range from 700 to 10 000 Da(P<0...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
Lucas S Torati, Hervé Migaud, Mary K Doherty, Justyna Siwy, Willian Mullen, Pedro E C Mesquita, Amaya Albalat
Parental investment in Arapaima gigas includes nest building and guarding, followed by a care provision when a cephalic fluid is released from the parents' head to the offspring. This fluid has presumably important functions for the offspring but so far its composition has not been characterised. In this study the proteome and peptidome of the cephalic secretion was studied in parental and non-parental fish using capillary electrophoresis coupled to mass spectrometry (CE-MS) and GeLC-MS/MS analyses. Multiple comparisons revealed 28 peptides were significantly different between males and parental males (PC-males), 126 between females and parental females (PC-females), 51 between males and females and 9 between PC-males and PC-females...
2017: PloS One
Douglas F Lake
The intracellular compartments for proteolytic antigen processing in tumor cells produce peptides that are presented by MHC molecules to T cells. But first, the ubiquitin ligase system tags defective, misfolded, aged, and unstable proteins for degradation through the proteasome. Ubiqitinated proteins are unfolded and fed into the barrel-shaped core of the proteasome where a collection of multiple different proteases cleave proteins into oligopeptides. After exiting the proteasome, these oligopeptides are either completely degraded into amino acids or trimmed at the N- and C-termini so that they bind to transporter associated with antigen processing (TAP)...
2017: Enzymes
David W Greening, Eugene A Kapp, Richard J Simpson
Peptides play a seminal role in most physiological processes acting as neurotransmitters, hormones, antibiotics, and immune regulation. In the context of tumor biology, it is hypothesized that endogenous peptides, hormones, cytokines, growth factors, and aberrant degradation of select protein networks (e.g., enzymatic activities, protein shedding, and extracellular matrix remodeling) are fundamental in mediating cancer progression. Analysis of peptides in biological fluids by mass spectrometry holds promise of providing sensitive and specific diagnostic and prognostic information for cancer and other diseases...
2017: Enzymes
Jia Fan, Bo Ning, Christopher J Lyon, Tony Y Hu
Mammalian proteases segregate into several distinct protein families that employ different functional domains to hydrolyze peptides bonds with different specificities and affinities. These enzymes play central roles in critical cellular and systemic processes, including regulation of cell growth, differentiation, homeostasis, and apoptosis; and cancer initiation, progression, and metastasis. Human proteases segregate into five distinct catalytic classes; the metalloprotease, serine protease, and cysteine protease families have the most members, while the aspartic and threonine peptidase families have relatively few examples...
2017: Enzymes
Kohei Kazuma, Keiichi Masuko, Katsuhiro Konno, Hidetoshi Inagaki
Ants (hymenoptera: Formicidae) have adapted to many different environments and have become some of the most prolific and successful insects. To date, 13,258 ant species have been reported. They have been classified into 333 genera and 17 subfamilies. Except for a few Formicinae, Dolichoderinae, and members of other subfamilies, most ant species have a sting with venom. The venoms are composed of formic acid, alkaloids, hydrocarbons, amines, peptides, and proteins. Unlike the venoms of other animals such as snakes and spiders, ant venoms have seldom been analyzed comprehensively, and their compositions are not yet completely known...
October 13, 2017: Toxins
Katerina Markoska, Martin Pejchinovski, Claudia Pontillo, Petra Zürbig, Lotte Jacobs, Andrew Smith, Jelka Masin-Spasovska, Olivera Stojceva-Taneva, Momir Polenakovic, Fulvio Magni, Harald Mischak, Goce Spasovski
Background: An improvement in the glomerular filtration rate (GFR) of chronic kidney disease patients has been an underestimated clinical outcome. Although this may be considered as an unexpected disease course, it may provide some insights into possible mechanisms underlying disease remission and/or regression. Therefore, our aim was to identify urinary peptide biomarkers associated with an improvement in estimated GFR (eGFR) over time and to improve patient stratification. Methods: Capillary electrophoresis coupled with mass spectrometry (CE-MS) was employed to evaluate the urine peptidome of patients with different types of renal diseases...
September 1, 2017: Nephrology, Dialysis, Transplantation
Benjamin L Parker, James G Burchfield, Daniel Clayton, Thomas A Geddes, Richard J Payne, Bente Kiens, Jørgen Wojtaszewski, Erik A Richter, David E James
Exercise is extremely beneficial to whole body health reducing the risk of a number of chronic human diseases. Some of these physiological benefits appear to be mediated via the secretion of peptide/protein hormones into the blood stream. The plasma peptidome contains the entire complement of low molecular weight endogenous peptides derived from secretion, protease activity and PTMs, and is a rich source of hormones. In the current study we have quantified the effects of intense exercise on the plasma peptidome to identify novel exercise regulated secretory factors in humans...
October 5, 2017: Molecular & Cellular Proteomics: MCP
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