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Peptide mimics

Dongliang Li, Shingo Toji, Kazue Watanabe, Toshihiko Torigoe, Tomohide Tsukahara
Osteosarcoma is the most common malignancy of bone that affects young people. Neoadjuvant chemotherapy and surgery have significantly improved the prognosis. However, the prognosis of non-responders to chemotherapy is still poor. To develop peptide-based immunotherapy for osteosarcoma, we previously identified CTL epitopes derived from papillomavirus binding factor (PBF) in the context of HLA-A2, HLA-A24 and HLA-B55. In the present study, we identified two novel CTL epitopes, QVT (QVTVWLLEQK) and LSA (LSALPPPLHK), in the context of HLA-A11 using a sequence of screenings based on the predicted affinity of peptides, in vitro folding ability of a peptide/HLA-A11 complex, reactivity of a peptide/HLA-A11 tetramer and IFN-γ production of T cells that was induced by mixed lymphocyte peptide culture under a limiting dilution condition...
February 15, 2019: Cancer Science
Fiona M Gribble, Frank Reimann
Gut hormones have many key roles in the control of metabolism, as they target diverse tissues involved in the control of intestinal function, insulin secretion, nutrient assimilation and food intake. Produced by scattered cells found along the length of the intestinal epithelium, gut hormones generate signals related to the rate of nutrient absorption, the composition of the luminal milieu and the integrity of the epithelial barrier. Gut hormones already form the basis for existing and developing therapeutics for type 2 diabetes mellitus and obesity, exemplified by the licensed glucagon-like peptide 1 (GLP1) mimetics and dipeptidyl peptidase inhibitors that enhance GLP1 receptor activation...
February 13, 2019: Nature Reviews. Endocrinology
Jingjing Xu, Franck Merlier, Bérangère Avalle, Vincent Vieillard, Patrice Debré, Karsten Haupt, Bernadette Tse Sum Bui
We describe the preparation and characterization of synthetic antibodies based on molecularly imprinted polymer nanoparticles (MIP-NPs), for the recognition and binding of the highly conserved and specific peptide motif SWSNKS (3S), an epitope of the envelope glycoprotein 41 (gp41) of human immunodeficiency virus type 1 (HIV-1). This motif is implicated in the decline of CD4+ T cells and leads to the deterioration of the immune system during HIV infection. Therefore, the development of MIP-NPs that can target and block the 3S peptide to prevent subsequent cascade interactions directed toward the killing of CD4+ T cells is of prime importance...
February 13, 2019: ACS Applied Materials & Interfaces
Mariano Larzábal, Hector A Baldoni, Fernando D Suvire, Lucrecia M Curto, Gabriela E Gomez, Wanderson Marques Da Silva, Silvana L Giudicessi, Silvia A Camperi, Jose M Delfino, Angel A Cataldi, Daniel Enriz
Human pathogenic gram-negative bacteria, such as enteropathogenic Escherichia coli (EPEC), rely on type III secretion systems (T3SS) to translocate virulence factors directly into host cells. The coiled-coil domains present in the structural proteins of T3SS are conformed by amphipathic alpha-helical structures that play an important role in the protein-protein interaction and are essential for the assembly of the translocation complex. To investigate the inhibitory capacity of these domains on the T3SS of EPEC, we synthesized peptides between 7 and 34 amino acids based on the coiled-coil domains of proteins that make up this secretion system...
February 11, 2019: Journal of Peptide Science: An Official Publication of the European Peptide Society
Arvind Soni, Chang Lin, Michael Murphy, Martin Eugene Tanner
The enzymes Csd6 and Pgp2 are peptidoglycan (PG) proteases found in the pathogenic bacteria Helicobacter pylori and Campylobacter jejuni, respectively. These enzymes are involved in the trimming of uncrosslinked PG sidechains and catalyze the cleavage of the bond between meso-diaminopimelic acid (meso-Dap) and D-alanine, thus converting a PG-tetrapeptide into a PG-tripeptide. They are known to be cell shape-determining enzymes, since deletion of the corresponding genes result in mutant strains that have lost the normal helical phenotype and instead possess a straight rod morphology...
February 11, 2019: Chembiochem: a European Journal of Chemical Biology
James R Wodicka, Vasilios A Morikis, Tima Dehghani, Scott I Simon, Alyssa Panitch
Introduction: The glycocalyx is a layer of glycoproteins, proteoglycans and glycosaminoglycans that coats the luminal surface of most blood vessels. It effectively regulates adhesive interactions between leukocytes in flowing blood and the endothelium, where during inflammation, binding to E- and P-selectins and intercellular adhesion molecule-1 (ICAM-1) promotes cell tethering and arrest under shear flow. Methods: In this study, we examine the targeting of E-selectin by an engineered peptide moiety bound to a dermatan sulfate backbone...
2019: Cellular and Molecular Bioengineering
Nan-Jie Gong, Russell Dibb, Marjolein Bulk, Louise van der Weerd, Chunlei Liu
Beta amyloid is a protein fragment snipped from the amyloid precursor protein (APP). Aggregation of these peptides into amyloid plaques is one of the hallmarks of Alzheimer's disease. MR imaging of beta amyloid plaques has been attempted using various techniques, notably with T2* contrast. The non-invasive detectability of beta amyloid plaques in MR images has so far been largely attributed to focal iron deposition accompanying the plaques. It is believed that the T2* shortening effects of paramagnetic iron are the primary source of contrast between plaques and surrounding tissue...
February 7, 2019: NeuroImage
Birthe Dorgau, Majed Felemban, Gerrit Hilgen, Martin Kiening, Darin Zerti, Nicola Claire Hunt, Mary Doherty, Phil Whitfield, Dean Hallam, Kathryn White, Yuchun Ding, Natalio Krasnogor, Jumana Al-Aama, Hani Z Asfour, Evelyne Sernagor, Majlinda Lako
Tissue specific extracellular matrices (ECM) provide structural support and enable access to molecular signals and metabolites, which are essential for directing stem cell renewal and differentiation. To mimic this phenomenon in vitro, tissue decellularisation approaches have been developed, resulting in the generation of natural ECM scaffolds that have comparable physical and biochemical properties of the natural tissues and are currently gaining traction in tissue engineering and regenerative therapies due to the ease of standardised production, and constant availability...
January 22, 2019: Biomaterials
João Medeiros-Silva, Shehrazade Jekhmane, Eefjan Breukink, Markus Weingarth
The alarming rise of antimicrobial resistance (AMR) imposes severe burdens on health care systems and the economy worldwide, urgently calling for the development of novel antibiotics. Antimicrobial peptides could be ideal templates for next-generation antibiotics due to their low propensity to develop resistance. An especially promising branch of antimicrobial peptides target Lipid II, the precursor of the bacterial peptidoglycan network. In order to develop these peptides into clinically applicable compounds, detailed information on their pharmacologically relevant modes of action is of critical importance...
February 6, 2019: Chembiochem: a European Journal of Chemical Biology
Pethaiah Gunasekaran, Ganesan Rajasekaran, Eun Hee Han, Young-Ho Chung, Young-Jin Choi, Yu Jin Yang, Ji Eun Lee, Hak Nam Kim, Kiram Lee, Jin-Seok Kim, Hyun-Jun Lee, Eun-Ju Choi, Eun-Kyung Kim, Song Yub Shin, Jeong Kyu Bang
The emergence of multi-drug resistant bacteria forces the therapeutic world into a position, where the development of new and alternative kind of antibiotics is highly important. Herein, we report the development of triazine-based amphiphilic small molecular antibacterial agents as mimics of lysine- and arginine-based cationic peptide antibiotics (CPAs). These compounds were screened against a panel of both Gram-positive and Gram-negative bacterial strains. Further, anti-inflammatory evaluation of these compounds led to the identification of four efficient compounds, DG-5, DG-6, DL-5, and DL-6...
February 4, 2019: Scientific Reports
Pamela C Rosato, Sathi Wijeyesinghe, J Michael Stolley, Christine E Nelson, Rachel L Davis, Luke S Manlove, Christopher A Pennell, Bruce R Blazar, Clark C Chen, Melissa A Geller, Vaiva Vezys, David Masopust
The immunosuppressive tumor microenvironment limits the success of current immunotherapies. The host retains memory T cells specific for previous infections throughout the entire body that are capable of executing potent and immediate immunostimulatory functions. Here we show that virus-specific memory T cells extend their surveillance to mouse and human tumors. Reactivating these antiviral T cells can arrest growth of checkpoint blockade-resistant and poorly immunogenic tumors in mice after injecting adjuvant-free non-replicating viral peptides into tumors...
February 4, 2019: Nature Communications
Caterina Maria Lombardo, Vasantha Kumar M V, Céline Douat, Frédéric Rosu, Jean-Louis Mergny, Gilmar F Salgado, Gilles Guichard
A number of foldamer backbones have been described as useful mimics of protein secondary structure elements, enabling for example the design of synthetic oligomers with the ability to engage specific protein surfaces. Synthetic folded backbones can also be used to create artificial proteins in which a folded peptide segment (e.g., an α-helix, a loop) is replaced by its unnatural counterpart, with the expectation that the resulting molecule would maintain its ability to fold while manifesting new exploitable features...
February 4, 2019: Journal of the American Chemical Society
Maria Baskin, Hui Zhu, Zheng-Wang Qu, Jordan H Chill, Stefan Grimme, Galia Maayan
Helices are key structural features in biopolymers, enabling a variety of biological functions. Mimicking these secondary structure motifs has wide potential in the development of biomimetic materials. Peptoids, N -substituted glycine oligomers, are an important class of peptide mimics that can adopt polyproline type helices if the majority of their sequence consists of chiral bulky pendent groups. Such side-chains are structure inducers but they have no functional value. We present here the inclusion of several metal-binding groups in one peptoid oligomer as a new platform towards the development of functional helical peptoids...
January 14, 2019: Chemical Science
Evgeniy S Salnikov, Christopher Aisenbrey, G M Anantharamaiah, Burkhard Bechinger
The membrane topology of the peptide 18 A, a derivative of apolipoprotein A-I, is investigated in structural detail. Apolipoprotein A-I is the dominant protein component of high density lipoproteins with important functions in cholesterol metabolism. 18 A (Ac-DWLKA FYDKV AEKLK EAF- NH2 ) was designed to mimic the structure of tandem domains of class A amphipathic helices and has served as a lead peptide for biomedical applications. At low peptide-to-lipid ratios 18 A partitions into phosphatidylcholine membranes with helix topologies parallel to the membrane surface, an alignment that is maintained when disc-like bicelles form at higher peptide-to-lipid ratios...
January 31, 2019: Chemistry and Physics of Lipids
Harinath Bahudhanapati, Jiangning Tan, Justin A Dutta, Stephen B Strock, John Sembrat, Diana Àlvarez, Mauricio Rojas, Benedikt Jäger, Antje Prasse, Yingze Zhang, Daniel J Kass
The hormone relaxin is considered a potential therapy for idiopathic pulmonary fibrosis (IPF). We have previously shown that a potential limitation to relaxin-based IPF therapy is decreased expression of a relaxin receptor, relaxin/insulin-like family peptide receptor 1 (RXFP1), in IPF fibroblasts. The mechanism that down-regulates RXFP1 in IPF remains unclear. To determine whether microRNAs (miRs) regulate RXFP1 gene expression, here we employed a bioinformatics approach to identify miRs predicted to target RXFP1 and identified a putative miR-144-3p target site in the RXFP1 mRNA...
February 1, 2019: Journal of Biological Chemistry
Jing Zhang, Zheng Gang Zhang, Mei Lu, Yi Zhang, Xia Shang, Michael Chopp
The death of mature oligodendrocytes (OLs) leads to demyelination in the central nervous system (CNS) and subsequently to functional deficits. Remyelination requires the differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating OLs, which in the CNS with neurodegenerative diseases such as multiple sclerosis (MS), is often inhibited. Among the inhibitors of OPC differentiation are toll-like receptor 2 (TLR2) and interleukin-1 receptor-associated kinase 1 (IRAK1) signaling, and both are negatively regulated by microRNA-146a (miR-146a)...
January 29, 2019: Neurobiology of Disease
Jahnu Saikia, Gaurav Pandey, Sajitha Sashidharan, Ferrin Antony, Harshal B Nemade, Sachin Kumar, Nitin Chaudhary, Vibin Ramakrishnan
Aggregation of β-amyloid peptides is a key event in the formative stages of Alzheimer's disease. Promoting folding and inhibiting aggregation was reported as an effective strategy in reducing Aβ-elicited toxicity. This study experimentally investigates the influence of the external electric field (EF) and magnetic field (MF) of varying strengths on the in-vitro fibrillogenesis of hydrophobic core sequence Aβ16-22 and its parent peptide Aβ1-42. Biophysical methods such as ThT fluorescence, static light scattering, Circular Dichroism (CD) and Infrared spectroscopy suggest that EF has a stabilizing effect on the secondary structure, initiating a conformational switch of Aβ16-22 and Aβ1-42 from beta to non-beta conformation...
February 1, 2019: ACS Chemical Neuroscience
Haruko Takahashi, Kenji Yumoto, Kazuma Yasuhara, Enrico T Nadres, Yutaka Kikuchi, Russell S Taichman, Kenichi Kuroda
The discovery of anticancer therapeutics effective in eliminating dormant cells is a significant challenge in cancer biology. Here, we describe new synthetic polymer-based anticancer agents that mimic the mode of action of anticancer peptides. These anticancer polymers developed here are designed to capture the cationic, amphiphilic traits of anticancer peptides. The anticancer polymers are designed to target anionic lipids exposed on the cancer cell surfaces and act by disrupting the cancer cell membranes...
January 31, 2019: Scientific Reports
Jianhua Peng, Jinwei Pang, Lei Huang, Budbazar Enkhjargal, Tongyu Zhang, Jun Mo, Pei Wu, Weilin Xu, Yuchun Zuo, Jun Peng, Gang Zuo, Ligang Chen, Jiping Tang, John H Zhang, Yong Jiang
White matter injury (WMI) is associated with motor deficits and cognitive dysfunctions in subarachnoid hemorrhage (SAH) patients. Therapeutic strategy targeting WMI would likely improve the neurological outcomes after SAH. Low-density lipoprotein receptor-related protein-1 (LRP1), a scavenger receptor of apolipoprotein E (apoE), is able to modulate microglia polarization towards anti-inflammatory M2 phenotypes during inflammatory and oxidative insult. In the present study, we investigated the effects of LRP1 activation on WMI and underlying mechanisms of M2 microglial polarization in a rat model of SAH...
January 23, 2019: Redox Biology
Akari Kumagai, Fernando G Dupuy, Zoran Arsov, Yasmene Elhady, Diamond Moody, Robert K Ernst, Berthony Deslouches, Ronald C Montelaro, Y Peter Di, Stephanie Tristram-Nagle
In an effort to provide new treatments for the global crisis of bacterial resistance to current antibiotics, we have used a rational approach to design several new antimicrobial peptides (AMPs). The present study focuses on 24-mer WLBU2 and its derivative, D8, with the amino acid sequence, RRWVRRVRRWVRRVVRVVRRWVRR. In D8, all of the valines are the d-enantiomer. We use X-ray low- and wide-angle diffuse scattering data to measure elasticity and lipid chain order. We show a good correlation between in vitro bacterial killing efficiency and both bending and chain order behavior in bacterial lipid membrane mimics; our results suggest that AMP-triggered domain formation could be the mechanism of bacterial killing in both Gram-positive and Gram-negative bacteria...
January 31, 2019: Soft Matter
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