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Stapled peptides

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https://www.readbyqxmd.com/read/28530606/effects-of-chemical-composition-and-baking-on-in-vitro-digestibility-of-proteins-in-breads-made-from-selected-gluten-containing-and-gluten-free-flours
#1
Tong Wu, Cheryl Taylor, Thomas Nebl, Ken Ng, Louise E Bennett
Breads prepared from cereal grains are a dietary staple, providing a significant proportion of daily energy, but not necessarily of dietary protein. However, good digestibility of proteins in bread is important to avoid potential immunogenic effects of undigested peptides, including for those gluten-intolerant. Four gluten-containing (white wheat, wholemeal wheat, spelt and rye) and four gluten-free (chick pea, lupin, buckwheat, amaranth) flours were used to make yeast-leavened breads standardized for protein...
October 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28500289/stapled-big3-helical-peptide-erap-potentiates-anti-tumour-activity-for-breast-cancer-therapeutics
#2
Tetsuro Yoshimaru, Keisuke Aihara, Masato Komatsu, Yosuke Matsushita, Yasumasa Okazaki, Shinya Toyokuni, Junko Honda, Mitsunori Sasa, Yasuo Miyoshi, Akira Otaka, Toyomasa Katagiri
Estradiol (E2) and the oestrogen receptor-alpha (ERα) signalling pathway play pivotal roles in the proliferative activity of breast cancer cells. Recent findings show that the brefeldin A-inhibited guanine nucleotide-exchange protein 3-prohibitin 2 (BIG3-PHB2) complex plays a crucial role in E2/ERα signalling modulation in breast cancer cells. Moreover, specific inhibition of the BIG3-PHB2 interaction using the ERα activity-regulator synthetic peptide (ERAP: 165-177 amino acids), derived from α-helical BIG3 sequence, resulted in a significant anti-tumour effect...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28497694/stapled-rgd-peptide-enables-glioma-targeted-drug-delivery-by-overcoming-multiple-barriers
#3
Huitong Ruan, Xishan Chen, Cao Xie, Beibei Li, Man Ying, Yu Liu, Mingfei Zhang, Xuesai Zhang, Changyou Zhan, Wuyuan Lu, Weiyue Lu
Malignant glioma, the most frequent and aggressive central nervous system (CNS) tumor, severely threatens human health. One reason for its poor prognosis and short survival is the presence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), which restrict the penetration of therapeutics into the brain at different stages of glioma. Herein, inspired by the peptide stapling technique, we designed a cyclic RGD ligand via an all-hydrocarbon staple (stapled RGD, sRGD) to facilitate BBB penetration while retaining the capacity of BBTB penetration and targeting ability to glioma cells...
May 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28496125/enhancing-specific-disruption-of-intracellular-protein-complexes-by-hydrocarbon-stapled-peptides-using-lipid-based-delivery
#4
D Thean, J S Ebo, T Luxton, Xue'Er Cheryl Lee, T Y Yuen, F J Ferrer, C W Johannes, D P Lane, C J Brown
Linear peptides can mimic and disrupt protein-protein interactions involved in critical cell signaling pathways. Such peptides however are usually protease sensitive and unable to engage with intracellular targets due to lack of membrane permeability. Peptide stapling has been proposed to circumvent these limitations but recent data has suggested that this method does not universally solve the problem of cell entry and can lead to molecules with off target cell lytic properties. To address these issues a library of stapled peptides was synthesized and screened to identify compounds that bound Mdm2 and activated cellular p53...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28481338/eating-glutinous-brown-rice-twice-a-day-for-8-weeks-improves-glycemic-control-in-japanese-patients-with-diabetes-mellitus
#5
T Nakayama, Y Nagai, Y Uehara, Y Nakamura, S Ishii, H Kato, Y Tanaka
OBJECTIVE: We recently reported that eating glutinous brown rice (GBR) for 1 day improved the whole-day glucose profile and postprandial plasma glucose level compared with eating white rice (WR) or standard brown rice. However, it was unknown whether eating GBR could maintain improvement of glycemic control for a longer period. Therefore, we evaluated the effect of GBR intake for 8 weeks on glycemic control in outpatients with diabetes mellitus. METHODS: This was an open-label randomized crossover study in outpatients with type 2 diabetes...
May 8, 2017: Nutrition & Diabetes
https://www.readbyqxmd.com/read/28436014/a-critical-assessment-of-the-synthesis-and-biological-activity-of-p53-hdm2-stapled-peptide-inhibitors
#6
Rike Wallbrecher, Patrick Chène, Stephan Ruetz, Therese Stachyra, Thomas Vorherr, Roland Brock
BACKGROUND AND PURPOSE: Helix stapling enhances the activity of peptides that interact with a target protein in a helical conformation. These staples are also supposed to change the pharmacokinetics of the molecules and promote cytoplasmic targeting. We scrutinized to which degree the pharmacokinetic characteristics are a function of the staple and differ from those of the standard cationic cell-penetrating peptide nonaarginine for a peptide inhibiting the interaction of p53 with the human double minute 2 (Hdm2) protein...
April 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28433781/prevalence-of-celiac-disease-autoimmunity-among-adolescents-and-young-adults-in-china
#7
Juanli Yuan, Chunyan Zhou, Jinyan Gao, Jingjing Li, Fenglian Yu, Jun Lu, Xin Li, Xiaozhong Wang, Ping Tong, Zhihua Wu, Anshu Yang, Yonghong Yao, Sarah Nadif, Heng Shu, Jiang Xu, Yujie Wu, Luud Gilissen, Hongbing Chen
BACKGROUND & AIMS: In China, epidemiological information on celiac disease autoimmunity is scarce and fragmented. We investigated the prevalence of celiac disease autoimmunity in the general Chinese population. METHODS: In a cross-sectional prospective study, 19,778 undiagnosed Chinese adolescents and young adults (16-25 years old) were recruited from consecutive new students who underwent routine physical examinations at 2 universities in Jiangxi, China from Sep...
April 19, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28425639/designing-dual-inhibitors-of-mdm2-mdmx-unexpected-coupling-of-water-with-gatekeeper-y100-99
#8
Xiong An Lee, Chandra Verma, Adelene Y L Sim
Mdm2 and MdmX share high structural similarity in their N-terminal domains, yet dual inhibitors are challenging to design due to differences in the conformations of the binding pockets, and notably of the proposed gatekeeper residue, Y100/99. Analysis of crystal structures and molecular dynamics (MD) simulations of complexes of Mdm2 and MdmX resulted in the identification of a water molecule with a long residence time that appears to be modulated by the conformation of Y100/99. These observations lead us to speculate that dual inhibitors either i) stabilize both Mdm2 and MdmX with Y100/99 in the open conformation typically seen in complexes of Mdm2 with p53, or ii) the dual inhibitors are agnostic to the conformation of Y100/99...
April 20, 2017: Proteins
https://www.readbyqxmd.com/read/28414223/diversity-oriented-stapling-yields-intrinsically-cell-penetrant-inducers-of-autophagy
#9
Leila Peraro, Zhongju Zou, Kamlesh M Makwana, Ashleigh E Cummings, Haydn L Ball, Hongtao Yu, Yu-Shan Lin, Beth Levine, Joshua A Kritzer
Autophagy is an essential pathway by which cellular and foreign material are degraded and recycled in eukaryotic cells. Induction of autophagy is a promising approach for treating diverse human diseases, including neurodegenerative disorders and infectious diseases. Here, we report the use of a diversity-oriented stapling approach to produce autophagy-inducing peptides that are intrinsically cell-penetrant. These peptides induce autophagy at micromolar concentrations in vitro, have aggregate-clearing activity in a cellular model of Huntington's disease, and induce autophagy in vivo...
May 9, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28388005/a-novel-methodology-for-the-incorporation-of-chiral-linkers-in-stapled-peptides
#10
Juan C Serrano, James Sipthorp, Wenshu Xu, Laura S Itzhaki, Steven V Ley
Stapled peptides have arisen as a new class of chemical probe and potential therapeutic agents to modulate protein-protein interactions. Here, we report the first two-component i,i+7 stapling methodology using two orthogonal, on-resin stapling reactions to incorporate linkers bearing a chiral center on a p53-derived stapled peptide. Post-stapling modifications to the staple chain were performed on-resin, enabling rapid access to various peptide derivatives from a single staple. The stapled peptides have increased helicity, protease stability and in vitro binding affinities to MDM2 compared to the unstapled peptide...
April 7, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28366833/molecular-characterization-of-fmrfamide-like-peptides-in-meloidogyne-graminicola-and-analysis-of-their-knockdown-effect-on-nematode-infectivity
#11
Chanchal Kumari, Tushar K Dutta, Sonam Chaudhary, Prakash Banakar, Pradeep K Papolu, Uma Rao
The rice root-knot nematode, Meloidogyne graminicola, seriously impairs the growth and yield of rice which is an important staple food worldwide. The disruption of neuropeptide signalling leading to attenuation in nematode behaviour and thereby perturbed infection, offers an attractive alternative to control nematodes. In this direction, the present study was aimed at mining of putative FMRFamide-like peptides (FLPs) from the transcriptomic dataset of M. graminicola followed by characterization of those FLPs via sequencing of PCR products, qRT-PCR and Southern hybridization analysis...
July 1, 2017: Gene
https://www.readbyqxmd.com/read/28358924/processing-and-targeting-of-proteins-derived-from-polyprotein-with-2a-and-lp4-2a-as-peptide-linkers-in-a-maize-expression-system
#12
He Sun, Ni Zhou, Hai Wang, Dafang Huang, Zhihong Lang
In the transformation of multiple genes, gene fusion is an attractive alternative to other methods, including sexual crossing, re-transformation, and co-transformation, among others. The 2A peptide from the foot-and-mouth disease virus (FMDV) causes the co-translational "cleavage" of polyprotein and operates in a wide variety of eukaryotic cells. LP4, a linker peptide that originates from a natural polyprotein occurring in the seed of Impatiens balsamina, can be split between the first and second amino acids in post-translational processing...
2017: PloS One
https://www.readbyqxmd.com/read/28345248/application-of-thiol-yne-thiol-ene-reactions-for-peptide-and-protein-macrocyclizations
#13
Yuanxiang Wang, Benjamin Bruno, Sean Cornillie, Jason Nogueira, Diao Chen, Thomas Cheatham, Carol Lim, Danny Chou
We report the application of thiol-yne/thiol-ene reactions to synthesize mono- and bicyclic stapled peptides and proteins. We first developed a thiol-ene based peptide stapling method in aqueous conditions. This method enabled us to efficiently staple recombinantly expressed coil-coiled proteins. The resulting stapled protein demonstrates higher stability in its secondary structure than the unstapled version. Furthermore, we performed a thiol-yne coupling by using an α,ω-diyne to react with two cysteine residues to synthesize a stapled peptide with two vinyl sulfide groups...
March 26, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28342286/switching-aurora-a-kinase-on-and-off-at-an-allosteric-site
#14
REVIEW
Richard Bayliss, Selena G Burgess, Patrick J McIntyre
Protein kinases are central players in the regulation of cell cycle and signalling pathways. Their catalytic activities are strictly regulated through post-translational modifications and protein-protein interactions that control switching between inactive and active states. These states have been studied extensively using protein crystallography, although the dynamic nature of protein kinases makes it difficult to capture all relevant states. Here, we describe two recent structures of Aurora-A kinase that trap its active and inactive states...
March 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28340032/osptr7-osnpf8-1-a-putative-peptide-transporter-in-rice-is-involved-in-dimethylarsenate-accumulation-in-rice-grain
#15
Zhong Tang, Yi Chen, Fei Chen, Yuchen Ji, Fang-Jie Zhao
Rice (Oryza sativa) is a major dietary source of arsenic (As) for the population consuming rice as their staple food. Rice grain contains both inorganic As and methylated As species, especially dimethyarsinate (DMA). DMA is highly mobile in long-distance translocation in plants, but the underlying mechanism remains unknown. In the present study, we showed that OsPTR7 (OsNPF8.1), a putative peptide transporter in rice, was permeable to DMA in Xenopus laevis oocytes. Transient expression of the OsPTR7-green fluorescent protein (GFP) in tobacco protoplasts showed that OsPTR7 was localized in the cell plasma membrane...
May 1, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28326635/structure-enabled-discovery-of-a-stapled-peptide-inhibitor-to-target-the-oncogenic-transcriptional-repressor-tle1
#16
Sally McGrath, Marcello Tortorici, Ludovic Drouin, Savade Solanki, Lewis Vidler, Isaac Westwood, Peter Gimeson, Rob vanMontfort, Swen Hoelder
TLE1 is an oncogenic transcriptional co-repressor that exerts its repressive effects through binding of transcription factors. Inhibition of this protein-protein interaction represents a putative cancer target but no small molecule inhibitors have been published for this challenging interface. In this manuscript, we report the structure enabled design and synthesis of a constrained peptide inhibitor of TLE1. Our design featured introduction of a four carbon atom linker into the peptide epitope found in many TLE1 binding partners...
March 22, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28278376/stapled-voltage-gated-calcium-channel-cav-%C3%AE-interaction-domain-aid-peptides-act-as-selective-protein-protein-interaction-inhibitors-of-cav-function
#17
Felix Findeisen, Marta Campiglio, Hyunil Jo, Fayal Abderemane-Ali, Christine H Rumpf, Lianne Pope, Nathan D Rossen, Bernhard E Flucher, William F DeGrado, Daniel L Minor
For many voltage-gated ion channels (VGICs), creation of a properly functioning ion channel requires the formation of specific protein-protein interactions between the transmembrane pore-forming subunits and cystoplasmic accessory subunits. Despite the importance of such protein-protein interactions in VGIC function and assembly, their potential as sites for VGIC modulator development has been largely overlooked. Here, we develop meta-xylyl (m-xylyl) stapled peptides that target a prototypic VGIC high affinity protein-protein interaction, the interaction between the voltage-gated calcium channel (CaV) pore-forming subunit α-interaction domain (AID) and cytoplasmic β-subunit (CaVβ)...
March 17, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28244676/what-is-gluten
#18
REVIEW
Jessica R Biesiekierski
Gluten is the main storage protein of wheat grains. Gluten is a complex mixture of hundreds of related but distinct proteins, mainly gliadin and glutenin. Similar storage proteins exist as secalin in rye, hordein in barley, and avenins in oats and are collectively referred to as "gluten." The objective was to discuss the biochemical and functional properties of the gluten proteins, including structure, sources, and dietary intakes. Literature was reviewed from food science and nutrition journals. The gluten protein networks vary because of different components and sizes, and variability caused by genotype, growing conditions, and technological processes...
March 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28192089/dynamic-phenylalanine-clamp-interactions-define-single-channel-polypeptide-translocation-through-the-anthrax-toxin-protective-antigen-channel
#19
Koyel Ghosal, Jennifer M Colby, Debasis Das, Stephen T Joy, Paramjit S Arora, Bryan A Krantz
Anthrax toxin is an intracellularly acting toxin where sufficient detail is known about the structure of its channel, allowing for molecular investigations of translocation. The toxin is composed of three proteins, protective antigen (PA), lethal factor (LF), and edema factor (EF). The toxin's translocon, PA, translocates the large enzymes, LF and EF, across the endosomal membrane into the host cell's cytosol. Polypeptide clamps located throughout the PA channel catalyze the translocation of LF and EF. Here, we show that the central peptide clamp, the ϕ clamp, is a dynamic site that governs the overall peptide translocation pathway...
February 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28182770/biochemical-and-biophysical-investigations-of-the-interaction-between-human-glucokinase-and-pro-apoptotic-bad
#20
Alix Rexford, Diego A R Zorio, Brian G Miller
The glycolytic enzyme glucokinase (GCK) and the pro-apoptotic protein BAD reportedly reside within a five-membered complex that localizes to the mitochondria of mammalian hepatocytes and pancreatic β-cells. Photochemical crosslinking studies using a synthetic analog of BAD's BH3 domain and in vitro transcription/translation experiments support a direct interaction between BAD and GCK. To investigate the biochemical and biophysical consequences of the BAD:GCK interaction, we developed a method for the production of recombinant human BAD...
2017: PloS One
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