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Janice M Reimer, Asfarul S Haque, Michael J Tarry, T Martin Schmeing
Nonribosomal peptide synthetases (NRPSs) produce peptide products with wide-ranging biological activities. NRPSs are macromolecular machines with modular assembly-line logic, a complex catalytic cycle, moving parts and multiple active sites. They are organized into repeating sets of domains, called modules. Each module contains all functionality to introduce a building block into the growing peptide, many also perform cosynthetic tailoring. Structures of individual domains have provided insights into their catalytic mechanisms, but with one exception, larger NRPS proteins were refractory to structure determination...
February 11, 2018: Current Opinion in Structural Biology
Yahya E Jad, Santosh Kumar Gudimella, Thavendran Govender, Beatriz G de la Torre, Fernando Albericio
The synthesis of pyrroles has received considerable attention because of their biological and pharmaceutical activities. Herein we describe a solid-phase multicomponent reaction that utilizes Lys as a N donor, β-nitrostyrenes, 1,3-dicarbonyl compounds, and FeCl3 as an easily accessible catalyst under microwave irradiation affords the subsequent pyrrole derivatives in high conversions. The strategy combines three of the most powerful tools in modern synthetic chemistry: the solid-phase mode, the microwave activation and a multicomponent reaction...
February 14, 2018: ACS Combinatorial Science
Laurie L Baggio, Bernardo Yusta, Erin E Mulvihill, Xiemin Cao, Catherine J Streutker, Jagdish Butany, Thomas P Cappola, Kenneth B Margulies, Daniel J Drucker
Glucagon-like peptide-1 receptor (GLP-1R) agonists, used to treat type 2 diabetes and obesity, reduce rates of myocardial infarction and cardiovascular death. The GLP-1R has been localized to the human sinoatrial node; however, its expression in ventricular tissue remains uncertain. Here we studied GLP-1R expression in the human heart using GLP-1R-directed antisera, quantitative PCR, reverse transcription PCR to detect full length mRNA transcripts, and in situ hybridization. GLP1R mRNA transcripts, encompassing the entire open reading frame, were detected in all four cardiac chambers from 15 hearts at levels approximating those detected in human pancreas...
February 12, 2018: Endocrinology
Elvin J Lauron, Liping Yang, Jabari I Elliott, Maria D Gainey, Daved H Fremont, Wayne M Yokoyama
Viruses have evolved mechanisms of MHCI inhibition in order to evade recognition by cytotoxic CD8+ T cells (CTLs), which is well-illustrated by our prior studies on cowpox virus (CPXV) that encodes potent MHCI inhibitors. Deletion of CPXV viral MHCI inhibitors markedly attenuated in vivo infection due to effects on CTL effector function, not priming. However, the CTL response to CPXV in C57BL/6 mice is dominated by a single peptide antigen presented by H-2Kb. Here we evaluated the effect of viral MHCI inhibition on immunodominant (IDE) and subdominant epitopes (SDE) as this has not been thoroughly examined...
February 2018: PLoS Pathogens
Remigiusz Worch, Anita Dudek, Joanna Krupa, Anna Szymaniec, Piotr Setny
Cleavage of hemagglutinin precursor (HA0) by cellular proteases results in the formation of two subunits, HA1 and HA2. The N-terminal fragment of HA2, named a fusion peptide (HAfp), possess a charged, amine N-terminus. It has been shown that the N-terminus of HAfp stabilizes the structure of a helical hairpin observed for a 23-amino acid long peptide (HAfp1-23), whose larger activity than HAfp1-20 has been demonstrated recently. In this paper, we analyze the effect of N-terminal charge on peptide-mediated fusion efficiency and conformation changes at the membrane interface by comparison with the corresponding N -acetylated peptides of 20- and 23-amino acid lengths...
February 14, 2018: International Journal of Molecular Sciences
Milena Deptuła, Anna Wardowska, Maria Dzierżyńska, Sylwia Rodziewicz-Motowidło, Michał Pikuła
During recent decades, the market for peptide-based drugs, including antimicrobial peptides, has vastly extended and evolved. These drugs can be useful in treatment of various types of disorders, e.g., cancer, autoimmune diseases, infections, and non-healing wounds. Although peptides are less immunogenic than other biologic therapeutics, they can still induce immune responses and cause allergies. It is important to evaluate the immunogenic and allergic potential of peptides before they are forwarded to the expensive stages of clinical trials...
February 14, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Cécile Campagne, Léa Ripoll, Floriane Gilles-Marsens, Graça Raposo, Cédric Delevoye
Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from endosomes to maturing melanosomes. Among the proteins controlling endosome-melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting and trafficking of TYRP1 to melanosomes. We identify here β1-adaptin AP-1 subunit-derived peptides of 5 amino acids that block the interaction of KIF13A with AP-1 in cells...
February 14, 2018: International Journal of Molecular Sciences
Arushi Prakash, Marcel D Baer, Christopher J Mundy, Jim Pfaendtner
Peptoids are peptide-mimetic biopolymers that are easy-to-synthesize and adaptable for use in drugs, chemical scaffolds, and coatings. However, there is insufficient information about their structural preferences and interactions with the environment in various applications. We conducted a study to understand the fundamental differences between peptides and peptoids using molecular dynamics simulations with semi-empirical (PM6) and empirical (AMBER) potentials, in conjunction with metadynamics enhanced sampling...
February 14, 2018: Biomacromolecules
Yury I Kostyukevich, Eugene N Nikolaev
We present the simple approach for the combination of different ion sources on a single mass spectrometer without any interference between them. Each ion source can be positioned as far as 1 meter from the mass spectrometer; ions are transported by the means of flexible cooper tubes, which are connected, to the separate inlet capillaries. Special valves enable switching channels on and off. Using this approach, we successfully combined native ESI (electrospray ionization), regular ESI, beta-electrons ionization and APPI (Atmospheric pressure photoionization) of thermally desorbed vapors of petroleum on a single mass spectrometer...
February 14, 2018: Analytical Chemistry
Martijn van Rosmalen, Yan Ni, Daan F M Vervoort, Remco Arts, Susann Katrina Julie Ludwig, Maarten Merkx
Monitoring the levels of therapeutic antibodies in individual patients would allow patient-specific dose optimization, with the potential for major therapeutic and financial benefits. Our group recently developed a new platform of bioluminescent sensor proteins (LUMABS; LUMinescent AntiBody Sensor) that allow antibody detection directly in blood plasma. In this study we targeted four clinically important therapeutic antibodies, the Her2-receptor targeting trastuzumab, the anti-CD20 antibodies rituximab and obinutuzumab, and the EGFR-blocking cetuximab...
February 14, 2018: Analytical Chemistry
Qian Cai, Yue Fei, Hong-Wei An, Xiao-Xiao Zhao, Yang Ma, Yong Cong, Liming Hu, Li-Li Li, Hao Wang
The survival of S. aureus inside phagocytes is considered to be the sticking point of long-term chronic inflammation. Here, we fabricate peptide-chlorophyll based photodynamic therapy (PDT) agents with 'sandwich' dimeric structure to enhance PDT effect and active targeting property to eliminate intracellular infections, which could be seen as prospective antibacterial agents for inflammation.
February 14, 2018: ACS Applied Materials & Interfaces
Ruchika Meel, Richard Nethononda, Elena Libhaber, Therese Dix-Peek, Ferande Peters, Mohammed Essop
BACKGROUND: In chronic rheumatic mitral regurgitation (CRMR), involvement of the myocardium in the rheumatic process has been controversial. Therefore, we sought to study the presence of fibrosis using late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) and biomarkers of collagen turnover in CRMR. METHODS: Twenty-two patients with CRMR underwent CMR and echocardiography. Serum concentrations of matrix metalloproteinase- 1 (MMP-1), tissue inhibitor of MMP-1 (TIMP- 1), MMP-1-to-TIMP-1 ratio, procollagen III N-terminal pro-peptide (PIIINP) and procollagen type IC peptide (PIP) were measured...
February 6, 2018: Cardiovascular Journal of Africa
Qingming Ma, Hao Yuan, Yang Song, Youchuang Chao, Sze Yi Mak, Ho Cheung Shum
Partitioning refers to the distribution of solute molecules in the two immiscible phases of a mixture of two solutions, such as an aqueous two-phase system (ATPS). The partitioning of RNA and peptide has been adjusted in situ to facilitate their assembly into intracellular membraneless organelles. Despite the immense potential of this approach in artificial systems, a partitioning-dependent assembly of macromolecules has been limited, due to the sophisticated processing associated with their in situ modification...
February 14, 2018: Soft Matter
Flor M Mendez, Felipe J Núñez, Rocío I Zorrilla-Veloz, Pedro R Lowenstein, Maria G Castro
Epigenetic modifications may be involved in the development and progression of glioma. Changes in methylation and acetylation of promoters and regulatory regions of oncogenes and tumor suppressors can lead to changes in gene expression and play an important role in the pathogenesis of brain tumors. Native chromatin immunoprecipitation (ChIP) is a popular technique that allows the detection of modifications or other proteins tightly bound to DNA. In contrast to cross-linked ChIP, in native ChIP, cells are not treated with formaldehyde to covalently link protein to DNA...
January 29, 2018: Journal of Visualized Experiments: JoVE
Melva Suarez Muñoz, Davide Confalonieri, Heike Walles, Elisabeth M W M van Dongen, Gudrun Dandekar
Tissue engineering is a promising field, focused on developing solutions for the increasing demand on tissues and organs regarding transplantation purposes. The process to generate such tissues is complex, and includes an appropriate combination of specific cell types, scaffolds, and physical or biochemical stimuli to guide cell growth and differentiation. Microcarriers represent an appealing tool to expand cells in a three-dimensional (3D) microenvironment, since they provide higher surface-to volume ratios and mimic more closely the in vivo situation compared to traditional two-dimensional methods...
February 7, 2018: Journal of Visualized Experiments: JoVE
Marylène Vandevenne, Mathieu Dondelinger, Sami Yunus, Astrid Freischels, Régine Freischels, Oscar Crasson, Noureddine Rhazi, Pierre Bogaerts, Moreno Galleni, Patrice Filée
Biosensors are becoming increasingly important and implemented in various fields such as pathogen detection, molecular diagnosis, environmental monitoring, and food safety control. In this context, we used β-lactamases as efficient reporter enzymes in several protein-protein interaction studies. Furthermore, their ability to accept insertions of peptides or structured proteins/domains strongly encourages the use of these enzymes to generate chimeric proteins. In a recent study, we inserted a single-domain antibody fragment into the Bacillus licheniformis BlaP β-lactamase...
February 1, 2018: Journal of Visualized Experiments: JoVE
Zehong Yang, Hua Zhuang, Hong Song, Ji Liu, Xiaojun Zhao, Wei Lin
BACKGROUND: Despite of intensive efforts, the tumor progression of ovarian cancer has not yet been fully understood. Various studies suggest that an effective experimental model system In Vitro to mimic microenvironment in vivo and the fabrication of cell pattern formation In Vitro are of great importance for the ovarian cancer research. METHODS: This study cultivates SKOV3, A2780 and A2780/DDP ovarian cancer cell lines in RADA16-I peptide hydrogel to obtain 3D-precultured cancer cells and fabricate a type of miniature cell pattern formation In Vitro on RADA16-I peptide nanofibercoated coverslip by in situ AFM analysis and chemosensitivity assay in vitro...
April 1, 2018: Journal of Nanoscience and Nanotechnology
Xiao-Ning Lin, Xinli Tian, Wang Li, Jin Sun, Feng Wei, Wei Feng, Zhi-Chun Huang, Xin-Hua Tian
Gliomas are the most common type of intracranial malignant tumor; however, current treatment approaches are often ineffective due to limited penetration of genes or drugs through the blood-brain barrier (BBB). Here we describe the synthesis of gelatin-siloxane nanoparticles (GS NPs) as candidate gene carriers through a two-step sol-gel process. To increase the efficiency of glioma targeting, human immunodeficiency virus-derived Tat, tumor-targeting aptamer (TTA)1, and polyethylene glycol (PEG) were conjugated to the GS NPs to generate Tat-TTA1-PEG-GS NPs...
April 1, 2018: Journal of Nanoscience and Nanotechnology
Tao Jiang, Ho-Man Kan, Komal Rajpura, Erica J Carbone, Yingcui Li, Kevin W-H Lo
Osteoarthritis is a severe and debilitating joint disease, which is characterized as results from damage and degeneration of the articular cartilage of the joint surfaces. The incidence of osteoarthritis is growing increasingly high while current treatment methods remain suboptimal. The major issue for current osteoarthritic medications is that patients frequently experience adverse, nonspecific side effects that are not a direct result of the specific pharmacological action of the drug. The treatment processes could be made more effective, safe, and comfortable if it were possible to deliver the drugs specifically to cartilage tissue...
April 1, 2018: Journal of Nanoscience and Nanotechnology
Gokila Devi Mathialagan, Narkunaraja Shanmugam
Diabetes, a chronic metabolic disorder associated with significantly accelerated rates of inflammation. Gold nanoparticle plays a crucial role in biomedical applications. We described the development of hetero-functionalized gold nanoparticles (hfAuNPs) for targeted selective gene silencing by RNAi interference. This hfAuNPs was developed by parallelly conjugating biotinylated ARE-siRNA (siRNA to Adenosine Uridine-rich elements) and biotinylated RAGE interacting-peptide (RIP) to streptavidin coated gold nanoparticles (aAuNPs) thus forms a complex that provides biocompatibility and functionality in a physiological environment...
May 1, 2018: Journal of Nanoscience and Nanotechnology
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