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https://www.readbyqxmd.com/read/28328206/ligand-induced-conformational-change-of-insulin-regulated-aminopeptidase-insights-on-catalytic-mechanism-and-active-site-plasticity
#1
Anastasia Mpakali, Emmanuel Saridakis, Karl Harlos, Yuguang Zhao, Paraskevi Kokkala, Dimitris Georgiadis, Petros Giastas, Athanasios Papakyriakou, Efstratios Stratikos
Insulin-regulated aminopeptidase (IRAP) is an enzyme with several important biological functions that is known to process a large variety of different peptidic substrates although the mechanism behind this wide specificity is not clearly understood. We describe a crystal structure of IRAP in complex with a recently developed bioactive and selective inhibitor at 2.53 Å resolution. In the presence of this inhibitor the enzyme adopts a novel conformation in which domains II and IV are juxtaposed, forming a hollow structure that excludes external solvent access to the catalytic center...
March 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28326133/versatile-synthesis-of-the-signaling-peptide-glorin
#2
Robert Barnett, Daniel Raszkowski, Thomas Winckler, Pierre Stallforth
We present a versatile synthesis of the eukaryotic signaling peptide glorin as well as glorinamide, a synthetic analog. The ability of these compounds to activate glorin-induced genes in the social amoeba Polysphondylium pallidum was evaluated by quantitative reverse transcription PCR, whereby both compounds showed bioactivity comparable to a glorin standard. This synthetic route will be useful in conducting detailed structure-activity relationship studies as well as in the design of chemical probes to dissect glorin-mediated signaling pathways...
2017: Beilstein Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28326005/bioactivity-of-food-peptides-biological-response-of-rats-to-bovine-milk-whey-peptides-following-acute-exercise
#3
Carolina Soares Moura, Pablo Christiano Barboza Lollo, Priscila Neder Morato, Eder Muller Risso, Jaime Amaya-Farfan
Background: Several physiologically beneficial effects of consuming a whey protein hydrolysate (WPH) have been attributed to the greater availability of bioactive peptides. Aims: The aim was to investigate the effect of four branched-chain amino acid- (BCAA-)containing dipeptides, present in WPH, on immune modulation, stimulation of HSP expression, muscle protein synthesis, glycogen content, satiety signals and the impact of these peptides on the plasma free amino acid profiles. Methods: The animals were divided in groups: control (rest, without gavage), vehicle (water), L-isoleucyl-L-leucine (lle-Leu), L-leucyl-L-isoleucine (Leu-lle), L-valyl-Lleucine (Val-Leu), L-leucyl-L-valine (Leu-Val) and WPH...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28325868/inositol-phosphates-and-phosphoinositides-activate-insulin-degrading-enzyme-while-phosphoinositides-also-mediate-binding-to-endosomes
#4
Eun Suk Song, HyeIn Jang, Hou-Fu Guo, Maria A Juliano, Luiz Juliano, Andrew J Morris, Emilia Galperin, David W Rodgers, Louis B Hersh
Insulin-degrading enzyme (IDE) hydrolyzes bioactive peptides, including insulin, amylin, and the amyloid β peptides. Polyanions activate IDE toward some substrates, yet an endogenous polyanion activator has not yet been identified. Here we report that inositol phosphates (InsPs) and phosphatdidylinositol phosphates (PtdInsPs) serve as activators of IDE. InsPs and PtdInsPs interact with the polyanion-binding site located on an inner chamber wall of the enzyme. InsPs activate IDE by up to ∼95-fold, affecting primarily Vmax The extent of activation and binding affinity correlate with the number of phosphate groups on the inositol ring, with phosphate positional effects observed...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28324021/endogenous-calcitonin-gene-related-peptide-regulates-lipid-metabolism-and-energy-homeostasis-in-male-mice
#5
Tian Liu, Akiko Kamiyoshi, Takayuki Sakurai, Yuka Ichikawa-Shindo, Hisaka Kawate, Lei Yang, Megumu Tanaka, Xian Xian, Akira Imai, Liuyu Zhai, Kazutaka Hirabayashi, Kun Dai, Keiya Tanimura, Teng Liu, Nanqi Cui, Kyoko Igarashi, Akihiro Yamauchi, Takayuki Shindo
Calcitonin gene-related peptide (CGRP) is a bioactive peptide produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene. CGRP is largely distributed in the cardiovascular and nervous systems, where it acts as a regulatory factor. CGRP is also expressed in organs and tissues involved in metabolic regulation, including white adipose tissue (WAT), where its function is largely unknown. In this study, we examined the effects of endogenous CGRP on metabolic function. When we administered a high-fat diet to CGRP knockout (CGRP-/-) and wild-type (WT) mice for 10 weeks, we observed that food intake did not differ between the two groups, but body weight and visceral fat weight were significantly lower in CGRP-/- mice...
January 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/28319811/protein-epitope-mimetic-macrocycles-as-biopharmaceuticals
#6
REVIEW
Anatol Luther, Kerstin Moehle, Eric Chevalier, Glenn Dale, Daniel Obrecht
Fully synthetic medium-sized macrocyclic peptides mimicking the key β-hairpin and α-helical protein epitopes relevant in many protein-protein interactions have emerged as a novel class of drugs with the potential to fill an important gap between small molecules and proteins. Conformationally stabilized macrocyclic scaffolds represent ideal templates for medicinal chemists to incorporate bioactive peptide and protein pharmacophores in order to generate novel drugs to treat diseases with high unmet medical need...
March 5, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28319665/synthesis-of-four-disulfide-insulin-analogs-via-sequential-disulfide-bond-formation
#7
Fangzhou Wu, John P Mayer, Vasily G Gelfanov, Fa Liu, Richard D DiMarchi
Naturally-occurring, multiple cysteine-containing peptides are a structurally unique class of compounds with a wide range of therapeutic and diagnostic applications. The development of reliable, and precise chemical methods for their preparation is of paramount importance to facilitate exploration of their utility. We report an efficient approach based on stepwise, sequentially directed disulfide bond formation, exemplified here by the synthesis of four-disulfide bond containing insulin analogs. The cysteine protections consisted of tert-butylthiol (StBu), thiol-trimethoxyphenyl (STmp), trityl (Trt), 4-methoxytrityl (Mmt), S-acetamidomethyl (Acm) and tert-butyl (tBu)...
March 20, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28317757/antihypertensive-peptides-from-animal-products-marine-organisms-and-plants
#8
REVIEW
Seung Yun Lee, Sun Jun Hur
Bioactive peptides from food proteins exert beneficial effects on human health, such as angiotensin-converting enzyme (ACE) inhibition and antihypertensive activity. Several studies have reported that ACE-inhibitory peptides can come from animal products, marine organisms, and plants-derived by hydrolyzing enzymes such as pepsin, chymotrypsin, and trypsin-and microbial enzymes such as alcalase, thermolysin, flavourzyme, and proteinase K. Different ACE-inhibitory effects are closely related with different peptide sequences and molecular weights...
August 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28317712/lc-esi-qtof-ms-identification-of-novel-antioxidant-peptides-obtained-by-enzymatic-and-microbial-hydrolysis-of-vegetable-proteins
#9
Elena Babini, Davide Tagliazucchi, Serena Martini, Lucilla Dei Più, Andrea Gianotti
Bioactive antioxidant peptides are more and more attracting the attention of food manufacturers for their potential to transform food in functional food, able to prevent a variety of chronic diseases associated with oxidative stress. In the present study proteins extracted from different vegetable sources (KAMUT® khorasan wheat, emmer, lupine and pea) were hydrolyzed with commercial enzymes and Lactobacillus spp. strains. Hydrolysates were separated by size exclusion chromatography and purified fractions were analyzed for their antioxidant activity...
August 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28317604/bioactive-properties-of-maillard-reaction-products-generated-from-food-protein-derived-peptides
#10
K Arihara, L Zhou, M Ohata
Food protein-derived peptides are promising food ingredients for developing functional foods, since various bioactive peptides are released from food proteins. The Maillard reaction, which plays an important role in most processed foods, generates various chemical components during processing. Although changes of amino acids or proteins and reduced sugars by the Maillard reaction have been studied extensively, such changes of peptides by the Maillard reaction are still not resolved enough. Since food protein-derived peptides are widely utilized in many processed foods, it deserves concern and research on the changes of peptides by the Maillard reaction in foods during processing or storage...
2017: Advances in Food and Nutrition Research
https://www.readbyqxmd.com/read/28317603/protein-hydrolysates-and-biopeptides-production-biological-activities-and-applications-in-foods-and-health-benefits-a-review
#11
M Nasri
In recent years, a great deal of interest has been expressed regarding the production, characterization, and applications of protein hydrolysates and food-derived biopeptides due to their numerous beneficial health effects. In this regard, research is mainly focused on investigating the therapeutic potential of these natural compounds. Based on their amino acids composition, sequences, hydrophobicity, and length, peptides released from food proteins, beyond their nutritional properties, can exhibit various biological activities including antihypertensive, antioxidative, antithrombotic, hypoglycemic, hypocholesterolemic, and antibacterial activities among others...
2017: Advances in Food and Nutrition Research
https://www.readbyqxmd.com/read/28317483/a-critical-review-of-bioactive-food-components-and-of-their-functional-mechanisms-biological-effects-and-health-outcomes
#12
Rosa Pérez-Gregorio, Jesús Simal-Gándara
BACKGROUND: Eating behaviours are closely related to some medical conditions potentially leading to death such as cancer, cardiovascular disease and diabetes. Healthy eating practices, maintaining a normal weight, and regular physical activity could prevent up to 80% of coronary heart disease, 90% of type-2 diabetes and one-third of all cancers[1]. METHOD: Over the last two decades, the food industry has invested much effort in research and development of healthier, more nutritious foods...
March 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28316472/peptide-analysis-and-the-bioactivity-of-whey-protein-hydrolysates-from-cheese-whey-with-several-enzymes
#13
Renda Kankanamge Chaturika Jeewanthi, Myeong Hee Kim, Na-Kyoung Lee, Yoh Chang Yoon, Hyun-Dong Paik
The aim of this study was identifying a suitable food grade enzymes to hydrolyze whey protein concentrates (WPCs), to give the highest bioactivity. WPCs from ultrafiltration retentate were adjusted to 35% protein (WPC-35) and hydrolyzed by enzymes, alcalase, α-chymotrypsin, pepsin, protease M, protease S, and trypsin at different hydrolysis times (0, 0.5, 1, 2, 3, 4, and 5 h). These 36 types of hydrolysates were analyzed for their prominent peptides β-lactoglobulin (β-Lg) and α-lactalbumin (α-La), to identify the proteolytic activity of each enzyme...
2017: Korean Journal for Food Science of Animal Resources
https://www.readbyqxmd.com/read/28315441/physico-chemical-characteristics-and-fibril-forming-capacity-of-carp-swim-bladder-collagens-and-exploration-of-their-potential-bioactive-peptides-by-in-silico-approaches
#14
Gaurav Kumar Pal, P V Suresh
This study explores the sustainable valorization of carp swim bladder by-products. The high-value molecule collagens were successfully extracted from carp swim bladder with a yield of∼60% (dry weight basis) and characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis, UV-spectrum and Fourier transform infrared spectroscopy. The extracted collagens showed the fibril-forming ability and high denaturation temperature (38-39°C). Furthermore, the extracted collagens subjected to preparing bioactive collagen hydrolysates with potential antioxidant activities...
March 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28304193/peptidomic-analysis-of-fetal-heart-tissue-for-identification-of-endogenous-peptides-involved-in-tetralogy-of-fallot
#15
Jingjing Zhang, Dong Liang, Qing Cheng, Li Cao, Yun Wu, Yan Wang, Shuping Han, Zhangbin Yu, Xianwei Cui, Tianhui Xu, Dingyuan Ma, Ping Hu, Zhengfeng Xu
Tetralogy of fallot (TOF) is one of the most prevalent types of congenital heart diseases. As a category of bioactive molecules, peptides have been proved to participate in various biological processes. However, the role of endogenous peptides in the pathogenesis of TOF has not been studied. In this study, we performed a comparative peptidomic profile in the fetal heart of TOF and the control group for the first time by liquid chromatography-tandem mass spectrometry. Our data demonstrated that a total of 201 peptides derived from 176 precursor proteins were differentially expressed in the heart tissues of TOF fetuses compared with normal controls, including 41 upregulated peptides and 160 downregulated peptides...
March 17, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28303477/effect-of-co-overexpression-of-nisin-key-genes-on-nisin-production-improvement-in-lactococcus-lactis-ls01
#16
Zhi-Jian Ni, Xiao-Yuan Zhang, Fei Liu, Miao Wang, Rong-Hua Hao, Pei-Xue Ling, Xi-Qiang Zhu
Nisin is a small antimicrobial peptide produced by several subset strains of Lactococcus lactis. To improve nisin yield in the producer L. lactis LS01, we proposed a successive fusion of nisA with nisRK and nisFEG into a single shuttle expression vector pMG36e under the control of the native strong constitutive promoter p32. Subsequently, the recombinant vectors were transplanted into the producer cell through electroporation. Nisin productivity was determined through sodium dodecyl sulfate-polyacrylamide gel electrophoresis and bioactivity assays...
March 16, 2017: Probiotics and Antimicrobial Proteins
https://www.readbyqxmd.com/read/28301077/application-of-methyl-bisphosphine-ligated-palladium-complexes-for-low-pressure-n-11-c-acetylation-of-peptides
#17
Thomas L Andersen, Patrik Nordeman, Heidi F Christoffersen, Hélène Audrain, Gunnar Antoni, Troels Skrydstrup
A mild and effective method is described for (11) C-labeling of peptides selectively at the N-terminal nitrogen or at internal lysine positions. The presented method relies on the use of specific biphosphine palladium-methyl complexes and their high reactivity towards amino-carbonylation of amine groups in the presence [(11) C]carbon monoxide. The protocol facilitates the production of native N-(11) C-acetylated peptides, without any structural modifications and has been applied to a selection of bioactive peptides...
March 16, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28299865/novel-short-antimicrobial-peptide-isolated-from-xenopus-laevis-skin
#18
Yu Zhang, Songcai Liu, Siming Li, Yunyun Cheng, Linyan Nie, Gang Wang, Chen Lv, Wenzhen Wei, Cheng Cheng, Feng Hou, Linlin Hao
A rich source of bioactive peptides, including a large number of antimicrobial peptides, has been found in amphibian skin. In this study, a novel short antimicrobial peptide was purified from Xenopus laevis skin and characterised through reversed-phase high-performance liquid chromatography, Edman degradation and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. The peptide was composed of six amino acids with a sequence of DEDLDE and thus named X. laevis antibacterial peptide-P2 (XLAsp-P2)...
March 16, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28299738/identification-of-protease-cleavage-sites-by-charge-based-enrichment-of-protein-n-termini
#19
Zon W Lai, Oliver Schilling
Differential proteolytic processing, for example by matrix metalloproteases (MMPs), has been recognized as an important hallmark in numerous pathological conditions. One crucial challenge in the present studies of proteases is system-wide identification of endogenous biological substrates. In this chapter, we highlight a robust method for the identification of bioactive substrates and their sites of MMP cleavage, as well as by other proteases and peptidases, in a system-wide manner. This approach enriches for putative protein N-termini by removal of internal peptides using a charge reversal strategy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28295347/the-relaxin-3-rxfp3-system-as-a-peptidergic-pathway-to-control-hypothalamic-neurons
#20
Marc Landry
Nearly every neuron in the brain secretes a bioactive peptide along with a conventional neurotransmitter such as GABA or Glutamate. Peptides seem to have preceded the 'classical' transmitters as the nervous system developed. This article is protected by copyright. All rights reserved.
March 10, 2017: Journal of Physiology
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