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https://www.readbyqxmd.com/read/27909427/biocombinatorial-synthesis-of-novel-lipopeptides-by-com-domain-mediated-reprogramming-of-the-plipastatin-nrps-complex
#1
Hongxia Liu, Ling Gao, Jinzhi Han, Zhi Ma, Zhaoxin Lu, Chen Dai, Chong Zhang, Xiaomei Bie
Both donors and acceptors of communication-mediating (COM) domains are essential for coordinating intermolecular communication within nonribosomal peptides synthetases (NRPSs) complexes. Different sets of COM domains provide selectivity, allowing NRPSs to utilize different natural biosynthetic templates. In this study, novel lipopeptides were synthesized by reprogramming the plipastatin biosynthetic machinery. A Thr-to-Asp point mutation was sufficient to shift the selectivity of the donor COM domain of ppsB toward that of ppsD...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27882474/effects-of-cck-8-and-cystathionine-%C3%AE-lyase-hydrogen-sulfide-system-on-acute-lung-injury-in-rats
#2
Fengjun Tian, Yiling Ling, Yuqin Chen, Zhiyong Wang
Acute lung injury (ALI) is mainly characterized by diffusive injuries to lung epithelium and increased permeability of alveolar-capillary membranes caused by various factors, which leads to pulmonary edema and pulmonary closure. Lipopolysaccharide (LPS), which is the main component of the cell wall of gram-negative bacteria, is one of the most important factors causing pulmonary infection and ALI. More and more reports have indicated that hydrogen sulfide (H2S) is closely correlated with ALI and has anti-inflammation function, while the specific mechanism needs further investigation...
November 24, 2016: Inflammation
https://www.readbyqxmd.com/read/27875906/the-therapeutic-effects-of-cholecystokinin-octapeptide-on-rat-liver-and-kidney-microcirculation-disorder-in-endotoxic-shock
#3
Dong Zhang, Hui Li, Jing Geng, Yingmin Li, Shujin Li, Chunling Ma, Bin Cong, Xiaojing Zhang
OBJECTIVES: Our previous studies demonstrated that pretreatment with cholecystokinin octapeptide (CCK-8) could alleviate endothelial cell injury and reverse abnormal vascular reactivity as well as reduce LPS-induced inflammation cascades, which suggested that CCK-8 plays a potential role in anti-endotoxic shock. The present study aimed to determine the therapeutic effects of CCK-8 on rat liver and kidney microcirculatory perfusion disorder under endotoxic shock (ES) conditions. MATERIALS AND METHODS: Sprague-Dawley rats were induced to lethal endotoxic shock by an injection of LPS...
November 22, 2016: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/27865351/quercetin-relaxes-guinea-pig-gallbladder-strips
#4
Loren Kline, Edward Karpinski
Quercetin, a phytoestrogen and flavonoid, relaxes intestinal and vascular smooth muscle. The purpose of this study was to determine if quercetin had an effect on gallbladder smooth muscle. An in vitro technique was used to determine the effects of quercetin on gallbladder strips and which system(s) mediated the relaxation. Paired t tests were used; differences between means of P < .05 were considered significant. Adding quercetin before cholecystokinin or KCl produced a significant (P < .001) decrease in the amount of tension (0...
October 2016: Nutrition Research
https://www.readbyqxmd.com/read/27855337/osteotropic-peptide-mediated-bone-targeting-for-photothermal-treatment-of-bone-tumors
#5
Yitong Wang, Jian Yang, Hongmei Liu, Xinyu Wang, Zhengjie Zhou, Quan Huang, Dianwen Song, Xiaopan Cai, Lin Li, Kaili Lin, Jianru Xiao, Peifeng Liu, Qiang Zhang, Yiyun Cheng
The treatment of bone tumors is a challenging problem due to the inefficient delivery of therapeutics to bone and the bone microenvironment-associated tumor resistance to chemo- and radiotherapy. Here, we developed a bone-targeted nanoparticle, aspartate octapeptide-modified dendritic platinum-copper alloy nanoparticle (Asp-DPCN), for photothermal therapy (PTT) of bone tumors. Asp-DPCN showed much higher affinity toward hydroxyapatite and bone fragments than the non-targeted DPCN in vitro. Furthermore, Asp-DPCN accumulated more efficiently around bone tumors in vivo, and resulted in a higher temperature in bone tumors during PTT...
November 9, 2016: Biomaterials
https://www.readbyqxmd.com/read/27832662/effects-of-exogenous-interleukin-9-on-the-growth-proliferation-and-activity-of-interstitial-cells-of-cajal-cultured-in-vitro
#6
Lei Huang, Baofeng Du, Yaoyao Gong, Hairong Xu, Jia Lu, Xinmin Si
OBJECTIVES: To evaluate the role of exogenous interleukin-9 (IL-9) in the growth, proliferation and activity of interstitial cells of Cajal (ICCs) cultured in vitro, and to assess its role in maintaining the functions of ICCs. METHODS: ICCs of murine gastric antrum were isolated and cultured in vitro. ICCs were identified with c-Kit and ANO1 immunofluorescent antibodies. Both fluorescence microscope and confocal microscopy were used to observe the effects of IL-9 on the growth, proliferation and activity of ICCs in cultured in vitro...
November 11, 2016: Digestion
https://www.readbyqxmd.com/read/27715017/radiosynthesis-and-preclinical-evaluation-of-18-f-fluoroglycosylated-octreotate-for-somatostatin-receptor-imaging
#7
Simone Maschauer, Marcus Heilmann, Carmen Wängler, Ralf Schirrmacher, Olaf Prante
Short synthetic octapeptide analogs derived from the native somatostatin peptides SST-14 and SST-28, namely octreotate (TATE) or octreotide (TOC), bind with high affinity to somatostatin receptors (sstr), mainly to subtypes 2 and 5, which are expressed in high density on neuroendocrine tumors (NET). Therefore, radiolabeled TATE or TOC derivatives represent highly valuable imaging probes for NET diagnosis by positron emission tomography (PET). The aim of our study was the development of an 18F-labeled octreotate analog as an alternative radiotracer for the clinically established 68Ga-DOTATOC and 68Ga-DOTATATE...
October 7, 2016: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/27713939/novel-tubulin-targeted-cell-penetrating-antimitotic-octapeptide
#8
Debmalya Bhunia, Saswat Mohapatra, Prashant Kurkute, Subhajit Ghosh, Batakrishna Jana, Prasenjit Mondal, Abhijit Saha, Gaurav Das, Surajit Ghosh
An antimitotic cell penetrating octapeptide containing single Arg amino acid is discovered, which strongly binds with the exchangeable GTP/GDP binding site of tubulin, inhibits tubulin polymerization, reduces kinesin driven microtubule motility, activates apoptotic and mitotic check point proteins, induces apoptotic death and significantly inhibits the multicellular tumor spheroid growth of HeLa cells.
October 18, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27634327/use-of-an-octapeptide-guanidiniocarbonylpyrrole-conjugate-for-the-formation-of-a-supramolecular-%C3%AE-helix-that-self-assembles-into-ph-responsive-fibers
#9
Mao Li, Marijana Radić Stojković, Martin Ehlers, Elio Zellermann, Ivo Piantanida, Carsten Schmuck
Peptides that adopt β-helix structures are predominantly found in transmembrane protein domains or in the lipid bilayer of vesicles. Constructing a β-helix structure in pure water has been considered difficult without the addition of membrane mimics. Herein, we report such an example; peptide 1 self-assembles into a supramolecular β-helix in pure water based on charge interactions between the individual peptides. Peptide 1 further showed intriguing transitions from small particles to helical fibers in a time-dependent process...
October 10, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27633684/peptide-therapeutics-and-the-pharmaceutical-industry-barriers-encountered-translating-from-the-laboratory-to-patients
#10
John Rafferty, Hema Nagaraj, Alice P McCloskey, Rawan Huwaitat, Simon Porter, Alyaa Albadr, Garry Laverty
Peptides are receiving increasing interest as clinical therapeutics. These highly tunable molecules can be tailored to achieve desirable biocompatibility and biodegradability with simultaneously selective and potent therapeutic effects. Despite challenges regarding up-scaling and licensing of peptide products, their vast clinical potential is reflected in the 60 plus peptide-based therapeutics already on the market, and the further 500 derivatives currently in developmental stages. Peptides are proving effective for a multitude of disease states including: type 2 diabetes (controlled using the licensed glucagon-like peptide-1 receptor liraglutide); irritable bowel syndrome managed with linaclotide (currently at approval stages); acromegaly (treated with octapeptide somostatin analogues lanreotide and octreotide); selective or broad spectrum microbicidal agents such as the Gram-positive selective PTP-7 and antifungal heliomicin; anticancer agents including goserelin used as either adjuvant or monotherapy for prostate and breast cancer, and the first marketed peptide derived vaccine against prostate cancer, sipuleucel-T...
September 9, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27629560/prnp-prion-protein-regulates-the-secretion-of-exosomes-modulating-cav1-caveolin-1-suppressed-autophagy
#11
Marcos V S Dias, Bianca L Teixeira, Bruna R Rodrigues, Rita Sinigaglia-Coimbra, Isabel Porto-Carreiro, Martín Roffé, Glaucia N M Hajj, Vilma R Martins
Prion protein modulates many cellular functions including the secretion of trophic factors by astrocytes. Some of these factors are found in exosomes, which are formed within multivesicular bodies (MVBs) and secreted into the extracellular space to modulate cell-cell communication. The mechanisms underlying exosome biogenesis were not completely deciphered. Here, we demonstrate that primary cultures of astrocytes and fibroblasts from prnp-null mice secreted lower levels of exosomes than wild-type cells. Furthermore, prnp-null astrocytes exhibited reduced MVB formation and increased autophagosome formation...
November 2016: Autophagy
https://www.readbyqxmd.com/read/27539647/novel-members-of-the-adipokinetic-hormone-family-in-beetles-of-the-superfamily-scarabaeoidea
#12
Gerd Gäde, Petr Šimek, Heather G Marco
Eight beetle species of the superfamily Scarabaeoidea were investigated with respect to peptides belonging to the adipokinetic hormone (AKH) family in their neurohemal organs, the corpora cardiaca (CC). The following beetle families are represented: Scarabaeidae, Lucanidae, and Geotrupidae. AKH peptides were identified through a heterospecific trehalose-mobilizing bioassay and by sequence analyses, using liquid chromatography coupled to positive electrospray mass spectrometry (LC-ESI-MS) and analysis of the tandem MS(2) spectra obtained by collision-induced dissociation...
August 18, 2016: Amino Acids
https://www.readbyqxmd.com/read/27539268/homooligomeric-%C3%AE-3-r-valine-peptides-transformation-between-c14-and-c12-helical-structures-induced-by-a-guest-aib-residue
#13
Basavalingappa Vasantha, Gijo George, Srinivasarao Raghothama, Padmanabhan Balaram
Novel helical, structures unprecedented in the chemistry of α-polypeptides, may be found in polypeptides containing β and γ amino acids. The structural characterization of C12 and C14 -helices in oligo β-peptides was originally achieved using conformationally constrained cyclic β-residues. This study explores the conformational characteristics of proteinogenic β(3) residues in homooligomeric sequences and addresses the issue of inducing a transition between C14 and C12 helices by the introduction of a guest α-residue...
August 19, 2016: Biopolymers
https://www.readbyqxmd.com/read/27537101/from-bulk-to-plasmonic-nanoparticle-surfaces-the-behavior-of-two-potent-therapeutic-peptides-octreotide-and-pasireotide
#14
Belén Hernández, Eduardo López-Tobar, Santiago Sanchez-Cortes, Yves-Marie Coïc, Bruno Baron, Alexandre Chenal, Sergei G Kruglik, Fernando Pflüger, Régis Cohen, Mahmoud Ghomi
Octreotide and pasireotide are two cyclic somatostatin analogues with an important clinical use in the treatment and diagnosis of neuroendocrine tumors. Herein, by the combined use of several techniques (UV-visible absorption, fluorescence, circular dichroism, ζ-potential, transmission electron microscopy, Raman scattering, surface-enhanced Raman scattering, and quantum mechanical calculations) we have followed the structural dynamics of these analogues in the bulk, as well as their binding sites on plasmonic (gold and silver) colloids...
September 21, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27518404/exploration-of-the-bf2-15-major-histocompatibility-complex-class-i-binding-motif-and-identification-of-cytotoxic-t-lymphocyte-epitopes-from-the-h5n1-influenza-virus-nucleoprotein-in-chickens
#15
Weijun Zhang, Qinghua Huang, Mei Lu, Fengzhu Zhu, Yan-Yan Huang, Shao-Hua Yang, Zhengjie Kong, Xiu-Mei Zhang, Chuan-Tian Xu
The binding motif of BF2*15 major histocompatibility complex (MHC) class I was explored by analyzing the interaction between an infectious bronchitis virus octapeptide and BF2*15, and the cytotoxic T lymphocyte (CTL) epitope from the nucleoprotein (NP) of H5N1 virus was identified using experimental methods. Computational methods, including homology modeling, molecular dynamics simulation, and molecular docking analysis, were used. The recombinant plasmid pCAGGS-NP was constructed, and NP expression was confirmed by indirect immunofluorescence and Western blot in transfected 293T cells...
November 2016: Archives of Virology
https://www.readbyqxmd.com/read/27512731/angiotensin-receptors-structure-function-signaling-and-clinical-applications
#16
Khuraijam Dhanachandra Singh, Sadashiva S Karnik
Angiotensinogen - a serpin family protein predominantly produced by the liver is systematically processed by proteases of the Renin Angiotensin system (RAS) generating hormone peptides. Specific cell surface receptors for at least three distinct angiotensin peptides produce distinct cellular signals that regulate system-wide physiological response to RAS. Two well characterized receptors are angiotensin type 1 receptor (AT1 receptor) and type 2 receptor (AT2 receptor). They respond to the octapeptide hormone angiotensin II...
June 2016: J Cell Signal
https://www.readbyqxmd.com/read/27493714/osteogenic-differentiation-of-human-mesenchymal-stem-cells-promotes-mineralization-within-a-biodegradable-peptide-hydrogel
#17
Luis A Castillo Diaz, Mohamed Elsawy, Alberto Saiani, Julie E Gough, Aline F Miller
An attractive strategy for the regeneration of tissues has been the use of extracellular matrix analogous biomaterials. Peptide-based fibrillar hydrogels have been shown to mimic the structure of extracellular matrix offering cells a niche to undertake their physiological functions. In this study, the capability of an ionic-complementary peptide FEFEFKFK (F, E, and K are phenylalanine, glutamic acid, and lysine, respectively) hydrogel to host human mesenchymal stem cells in three dimensions and induce their osteogenic differentiation is demonstrated...
January 2016: Journal of Tissue Engineering
https://www.readbyqxmd.com/read/27475306/increased-activation-of-the-tresk-k-channel-mediates-vago-vagal-reflex-malfunction-in-diabetic-rats
#18
Gintautas Grabauskas, Xiaoyin Wu, Il Song, Shi-Yi Zhou, Thomas Lanigan, Chung Owyang
BACKGROUND & AIMS: Patients with diabetes have defects in the vagal afferent pathway that result in abnormal gastrointestinal function. We investigated whether selective increased activation of the 2 pore domain potassium channel TRESK contributes to nodose ganglia (NG) malfunction, disrupting gastrointestinal function in diabetic rats. METHODS: We conducted whole-cell current-clamp and single-unit recordings in NG neurons from diabetes-prone BioBreeding/Worcester rats and streptozotocin-induced diabetic (STZ-D) rats and compared with control rats...
July 27, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27447563/the-mitotic-tensegrity-guardian-tau-protects-mammary-epithelia-from-katanin-like1-induced-aneuploidy
#19
Haruka Sudo, Kazunori Nakajima
The microtubule associated-protein tau has been identified as an effective positive prognostic indicator in breast cancer. To explore the physiological function of tau in early carcinogenesis, endogenous tau was knocked down in primary cultured human mammary epithelial cells. This resulted in chromosome-bridging during anaphase followed by micronucleation, both of which were suppressed by a further katanin-like1 knockdown. We also detected that the exogenously expressed katanin-like1 induction of cellular transformation is prevented by exogenous tau in rat fibroblasts...
July 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27443979/targeting-the-sh3-domain-of-human-osteoclast-stimulating-factor-with-rationally-designed-peptoid-inhibitors
#20
Shijie Han, Qian Liu, Feng Wang, Zenong Yuan
Human osteoclast-stimulating factor (hOSF) is an intracellular protein produced by osteoclasts that induces osteoclast formation and bone resorption. The protein contains a modular Src homology 3 (SH3) domain that mediates the intermolecular recognition and interaction of hOSF with its biological partners. Here, we proposed targeting the hOSF SH3 domain to disrupt hOSF-partner interactions for bone disease therapy by using SH3 inhibitors. In the procedure, the primary sequences of three known hOSF-interacting proteins (c-Src, SMN and Sam68) were parsed, from which totally 31 octapeptide segments that contain the core SH3-binding motif PXXP were extracted, and their binding behavior to hOSF SH3 domain was investigated at structural level using a biomolecular modeling protocol...
August 2016: Journal of Peptide Science: An Official Publication of the European Peptide Society
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