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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
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
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
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
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...
September 14, 2016: Autophagy
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
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
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
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
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
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
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
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
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
Madhusudana M B Reddy, Krishnayan Basuroy, Subrayashastry Aravinda, Padmanabhan Balaram
The solid-state conformations of two αγ hybrid peptides Boc-[Aib-γ(4) (R)Ile]4 -OMe 1 and Boc-[Aib-γ(4) (R)Ile]5 -OMe 2 are described. Peptides 1 and 2 adopt C12 -helical conformations in crystals. The structure of octapeptide 1 is stabilized by six intramolecular 4 → 1 hydrogen bonds, forming 12 atom C12 motifs. The structure of peptide 2 reveals the formation of eight successive C12 hydrogen-bonded turns. Average backbone dihedral angles for αγ C12 helices are peptide 1, Aib; φ (°) = -57...
August 2016: Journal of Peptide Science: An Official Publication of the European Peptide Society
Akihiro Ninomiya, Yohei Katsuyama, Takefumi Kuranaga, Masayuki Miyazaki, Yuichi Nogi, Shigeru Okada, Toshiyuki Wakimoto, Yasuo Ohnishi, Shigeki Matsunaga, Kentaro Takada
Genome mining is a powerful method for finding novel secondary metabolites. In our study on the biosynthetic gene cluster for the cyclic octapeptides surugamides A-E (inhibitors of cathepsin B), we found a putative gene cluster consisting of four successive non-ribosomal peptide synthetase (NRPS) genes, surA, surB, surC, and surD. Prediction of amino acid sequence based on the NRPSs and gene inactivation revealed that surugamides A-E are produced by two NRPS genes, surA and surD, which were separated by two NRPS genes, surB and surC...
September 15, 2016: Chembiochem: a European Journal of Chemical Biology
Federica Novelli, Serena De Santis, Pasqualina Punzi, Cesare Giordano, Anita Scipioni, Giancarlo Masci
The preparation and structural organisation of new bioinspired nanomaterials based on regular alternating enantiomeric sequence of tetra- and hexapeptides end-linked to poly(ethylene glycol) (PEG) is reported. The peptide moiety is composed of two or three repeats of l-Ala-d-Val units while the PEG has a molecular weight of 2kDa. The self-assembling properties of the two conjugates depend significantly on the length of the peptide. Nanoparticles with different sizes and morphologies are formed, the structural properties of which are compared with the previously studied l-Ala-d-Val octapeptide conjugate that self-assembles into rod-like nanoparticles...
July 15, 2016: New Biotechnology
Zhong-Hou Rong, Hong-Yuan Chen, Xin-Xing Wang, Zhi-Yi Wang, Guo-Zhe Xian, Bang-Zhen Ma, Cheng-Kun Qin, Zhen-Hai Zhang
AIM: To investigate the mechanisms and effects of sphincter of Oddi (SO) motility on cholesterol gallbladder stone formation in guinea pigs. METHODS: Thirty-four adult male Hartley guinea pigs were divided randomly into two groups, the control group (n = 10) and the cholesterol gallstone group (n = 24), which was sequentially divided into four subgroups with six guinea pigs each according to time of sacrifice. The guinea pigs in the cholesterol gallstone group were fed a cholesterol lithogenic diet and sacrificed after 3, 6, 9, and 12 wk...
June 28, 2016: World Journal of Gastroenterology: WJG
Debajyoti Basak, Sucheta Sridhar, Amal K Bera, Nandita Madhavan
Synthetic pores that selectively transport ions of biological significance through membranes could be potentially used in medical diagnostics or therapeutics. Herein, we report cation-selective octapeptide pores derived from alanine and aminopicolinic acid. The ion transport mechanism through the pores has been established to be a cation-chloride symport. The cation-chloride co-transport is biologically essential for the efficient functioning of the central nervous system and has been implicated in diseases such as epilepsy...
May 18, 2016: Organic & Biomolecular Chemistry
Christine M Martin, Vadivel Parthsarathy, Annie Hasib, Ming T Ng, Stephen McClean, Peter R Flatt, Victor A Gault, Nigel Irwin
Xenin is a peptide that is co-secreted with the incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), from intestinal K-cells in response to feeding. Studies demonstrate that xenin has appetite suppressive effects and modulates glucose-induced insulin secretion. The present study was undertaken to determine the bioactivity and antidiabetic properties of two C-terminal fragment xenin peptides, namely xenin 18-25 and xenin 18-25 Gln. In BRIN-BD11 cells, both xenin fragment peptides concentration-dependently stimulated insulin secretion, with similar efficacy as the parent peptide...
2016: PloS One
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