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Anti cancer peptide

Juan Xu, Xusu Wang, Pengfei Xu, Siyu Liu, Fang Teng, Xiaoguang Liu, Qiaoying Zhu, Xiangdong Hua, Zhen Gong, Xuemei Jia
BACKGROUND: Bioactive peptides existing in vivo have been considered an important class of natural medicines for the treatment of diseases. Peptidome analysis of tissues and biofluids had provided important information about the differentially expressed bioactive peptides in vivo. METHODS: Here, we analyzed the peptidome of serous ovarian cancer tissue samples and normal ovarian epithelial tissue samples by mass spectrometry and further investigated the possible bioactive peptides that were differentially expressed...
December 10, 2018: International Journal of Biochemistry & Cell Biology
Li Zhang, Xiaoyu Zhu, Shijia Wu, Yazhou Chen, Shiming Tan, Yingjie Liu, Wenzheng Jiang, Jing Huang
Background: cis-Dichlorodiamineplatinum (CDDP) was one of the most common used drugs in clinic for cancer treatment. However, CDDP caused a variety of side effects. The abundant carboxyl groups on the surface of poly glutamic acid (PGA) could be modified with various kinds of targeted ligands. PGA delivery system loaded CDDP for cancer therapies possesses potential to overcome the side effects. Materials and methods: In this study, we constructed a safe and efficient anticancer drug delivery system PGA-Asp-maleimide-cisplatin-peptide complex (PAMCP), which was loaded with CDDP and conjugated with the transferrin receptor (TFR)-targeting peptide through a maleimide functional linker...
2018: International Journal of Nanomedicine
Yu Sakurai, Tomoya Hada, Akari Kato, Yuta Hagino, Wataru Mizumura, Hideyoshi Harashima
Although metastatic cancer is a major cause of death for cancer patients, no efficacious treatment for metastasis is available. We previously showed that the growth of a primary tumor could be inhibited by the administration of an anti-angiogenic small interfering RNA (siRNA) that is encapsulated in an RGD peptide-modified lipid nanoparticle (RGD-LNP). We herein report on the delivery of siRNA by an RGD-LNP to the vasculature is also effective for treating metastatic tumors. We compared the RGD-LNP with the polyethylene glycol (PEG)ylated LNP (PEG-LNP) in terms of accumulation in a lung-metastasized model...
December 21, 2018: Molecular Therapy Oncolytics
Tatjana Bilich, Annika Nelde, Leon Bichmann, Malte Roerden, Helmut R Salih, Daniel J Kowalewski, Heiko Schuster, Chih-Chiang Tsou, Ana Marcu, Marian C Neidert, Maren Lübke, Jonas Rieth, Mirle Schemionek, Tim H Brümmendorf, Vladan Vucinic, Dietger Niederwieser, Jens Bauer, Melanie Märklin, Janet K Peper, Reinhild Klein, Oliver Kohlbacher, Lothar Kanz, Hans-Georg Rammensee, Stefan Stevanović, Juliane S Walz
Anti-leukemia immunity plays an important role in disease control and maintenance of tyrosine kinase inhibitor (TKI)-free remission in chronic myeloid leukemia (CML). Thus, antigen-specific immunotherapy holds promise to strengthen immune control in CML, but requires the identification of CML-associated targets. In this study, we used a mass spectrometry-based approach to identify naturally presented, HLA class I- and class II-restricted peptides in primary CML samples. Comparative HLA ligandome profiling using a comprehensive dataset of different hematological benign specimen and samples of CML patients in deep molecular remission delineated a panel of novel, frequently presented, CML-exclusive peptides...
December 10, 2018: Blood
Aarti Anantram, Harish Kundaikar, Mariam Degani, Arati Prabhu
Inhibition of normal cellular apoptosis or programed cell death is the hallmark of all cancers. Apoptotic dysregulation can result in numerous pathological conditions, such as cancers, autoimmune disorders, and neurodegeneration. Members of the BCL-2 family of proteins regulate the process of apoptosis by its promotion or inhibition and overexpression of the pro-survival anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1) has been associated with tumor maintenance, growth and progression Small molecules and peptides which bind the BH3 binding groove of these proteins have been explored in the recent times for their anticancer potential...
December 10, 2018: Journal of Biomolecular Structure & Dynamics
Hyungjun Kim, Do Been Hwang, Minsuk Choi, Soyoung Lee, Sukmo Kang, Yonghyun Lee, Sunghyun Kim, Junho Chung, Sangyong Jon
A number of cancer-targeting peptide-drug conjugates (PDCs) have been explored as alternatives to antibody-drug conjugates (ADCs) for targeted cancer therapy. However, the much shorter circulation half-life of PDCs compared with ADCs in vivo has limited their therapeutic value and thus their translation into the clinic, highlighting the need to develop new approaches for extending the half-life of PDCs. Here, we report a new strategy for targeted cancer therapy of a PDC based on a molecular hybrid between an anti-hapten antibody and a hapten-labeled PDC...
December 6, 2018: Molecular Pharmaceutics
May Bakail, Silvia Rodriguez-Marin, Zsófia Hegedüs, Marie E Perrin, Françoise Ochsenbein, Andrew John Wilson
Inhibition of the histone H3-ASF1 (anti-silencing function 1) protein-protein interaction (PPI) represents a potential approach for treatment of numerous cancers. As an α-helix mediated PPI, constraint of the key histone H3 helix (residues 118-135) represents a strategy through which chemical probes might be elaborated to test this hypothesis. In this work variant H3118-135 peptides bearing pentenyl glycine residues at i and i + 4 positions were constrained by olefin metathesis. Biophysical analyses revealed that promotion of a bioactive helical conformation depends on the position at which the constraint is introduced, but that potency of binding towards ASF1 is unaffected by the constraint and instead that enthalpy-entropy compensation occurs...
December 4, 2018: Chembiochem: a European Journal of Chemical Biology
Dinusha Jinasena, Robert H Simmons, Nicholas C Fitzkee
Pin1 is an essential Peptidyl-prolyl isomerase (PPIase) that catalyzes cis-trans prolyl isomerization in proteins containing pSer/Thr-Pro motifs. It has an N-terminal WW domain that targets these motifs and a C-terminal PPIase domain that catalyzes isomerization. Recently, Pin1 was shown to modify the conformation of phosphorylated histone H1 and stabilize the chromatin-H1 interaction by increasing its residence time. This Pin1/histone H1 interaction plays a key role in pathogen response, in infection, and in cell cycle control; therefore, anti-Pin1 therapeutics are an important focus for treating infections as well as cancer...
December 3, 2018: Biochemistry
Robert Pola, Vlastimil Král, Sergey K Filippov, Leonid Kaberov, Tomáš Etrych, Irena Sieglova, Juraj Sedlacek, Milan Fábry, Michal Pechar
A water-soluble polymer cancerostatic actively targeted against cancer cells expressing a disialoganglioside antigen GD2 was designed, synthesized and characterized. A polymer conjugate of an anti-tumor drug doxorubicin with a N-(2-hydroxypropyl)methacrylamide-based copolymer was specifically targeted against GD2 antigen-positive tumor cells using a recombinant single chain fragment (scFv) of an anti-GD2 monoclonal antibody. The targeting protein ligand was attached to the polymer-drug conjugate either via a covalent bond between the amino groups of the protein using a traditional non-specific aminolytic reaction with a reactive polymer precursor or via a non-covalent but highly specific interaction between bungarotoxin covalently linked to the polymer and the recombinant scFv modified with a C-terminal bungarotoxin-binding peptide...
November 28, 2018: Biomacromolecules
Muhammad Ibrahim Rashid, Amjad Ali, Saadia Andleeb
Dual Oxidase 1 (DUOX1) is a prominent immune system component primarily expressed in esophagus, lungs, skin, and urinary bladder including others. DUOX1 is involved in lactoperoxidase-mediated innate immunity at mucosal surfaces by generation of antimicrobial hypothiocyanite at the apical surface of epithelial lining. Upon detection of bacterial pathogens mainly Pseudomonas aeruginosa, DUOX1 is activated in bronchial epithelial cells. Both the host and pathogen enter a redox dual with DUOX1 and hypothiocyanite from host and Pyocyanin (PCN) as a redox active virulence factor from P...
November 27, 2018: Interdisciplinary Sciences, Computational Life Sciences
Lin Cui, Yuli Wang, Meng Liang, Xiaoyang Chu, Shiyao Fu, Chunsheng Gao, Qianqian Liu, Wei Gong, Meiyan Yang, Zhiping Li, Lian Yu, Chunrong Yang, Zhide Su, Xiangyang Xie, Yang Yang, Chunsheng Gao
Therapeutic outcome for the treatment of glioma was often limited due to the two barriers involved: the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). Therefore, the development of nanocarriers that possess both BBB and BBTB permeability and glioma-targeting ability is of great importance for the chemotherapy of glioma. New frontiers in nanomedicine are advancing the research of new biomaterials. Here we constructed a natural high-density lipoprotein particle (HDL)-based drug delivery system with the dual-modification of T7 and d A7R peptide ligand (T7/d A7R-HDL) to achieve the above goals...
November 2018: Drug Delivery
Jin Ma, Ke Kang, Yujia Zhang, Qiangying Yi, Zhongwei Gu
In this work, we presented the ternary nanoparticles [pCBMA(CD-D/DOX)] based on peptide dendritic carbon dots (CDs) to realize tumor-specific drug delivery and high efficient cancer therapy. The versatile nanoparticles could achieve "stealth" delivery in blood due to the anti-fouling zwitterion coating. Meanwhile, charge changes of the zwitterions could be moderated during their transportation toward/inside tumor cells, where subtle environmental pH variations acted as potent stimuli to actualize desired functions...
November 26, 2018: ACS Applied Materials & Interfaces
Sadaomi Sugimoto, Hiroshi Maeda, Mizuki Kitamatsu, Ikuo Nishikawa, Muneyasu Shida
Peptide nucleic acids (PNA) are DNA/RNA analogs in which the sugar-phosphate backbone is replaced by N-2-aminoethylglycine. PNA are widely used for experimental antisense therapy due to their strong affinity to mRNA. By targeting specific genes, protein synthesis and the growth of bacteria or cancer cells can be inhibited by PNA. Here, we report the design and evaluation of antisense PNA for selective growth inhibition of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, potent pathogens associated with periodontitis...
November 21, 2018: Molecular and Cellular Probes
Chen-Hung Ting, Yi-Chung Liu, Ping-Chiang Lyu, Jyh-Yih Chen
Some antimicrobial peptides (AMPs) exhibit anti-cancer activity, acting on cancer cells either by causing membrane lysis or via intracellular effects. While intracellular penetration of AMPs has been shown to cause cancer cell death, the mechanisms of toxicity remain largely unknown. Here we show that a tilapia-derived AMP, Tilapia piscidin (TP) 4, penetrates intracellularly and targets the microtubule network. A pull-down assay identified α-Tubulin as a major interaction partner for TP4, and molecular docking analysis suggested that Phe1, Ile16, and Arg23 on TP4 are required for the interaction...
November 22, 2018: Marine Drugs
Laurent M Paardekooper, Maura B Bendix, Andrea Ottria, Lieke W de Haer, Martin Ter Beest, Timothy Rdj Radstake, Wioleta Marut, Geert van den Bogaart
Dendritic cells (DCs) constantly sample peripheral tissues for antigens, which are subsequently ingested to derive peptides for presentation to T-cells in lymph nodes. To do so, DCs have to traverse many different tissues with varying oxygen tensions. Additionally, DCs are often exposed to low oxygen tensions in tumors, where vascularization is lacking, as well as in inflammatory foci, where oxygen is rapidly consumed by inflammatory cells during the respiratory burst. DCs respond to oxygen levels to tailor immune responses to such low-oxygen environments...
November 21, 2018: Bioscience Reports
Sindy Vrecko, David Guenat, Patricia Mercier-Letondal, Hugues Faucheu, Magalie Dosset, Bernard Royer, Jeanne Galaine, Romain Boidot, Stefano Kim, Marine Jary, Olivier Adotévi, Christophe Borg, Yann Godet
Sorafenib, a multi-targeted kinase inhibitor, is the current standard systemic treatment for advanced hepatocellular carcinoma. Sorafenib has anti-angiogenic and anti-proliferative properties and is also known to favor anti-tumor T cell responses by reducing the population of immunosuppressive cells such as Treg and MDSC. Anti-tumor immune responses, especially mediated by CD4+ T-cells, are critical for tumor cells eradication and therapies modulating those responses are appealing in a growing number of cancers...
October 23, 2018: Oncotarget
Jun Xu, Shuo Chen, Jing Jin, Lingman Ma, Min Guo, Changlin Zhou, Jie Dou
Influenza A virus is a leading cause of mortality in humans and poses a global health emergency due to its newly adapted and resistant strains. Thus, there is an urgency to develop novel anti-influenza drugs. Peptides are a type of biological molecule having a wide range of inhibitory effects against bacteria, fungi, viruses and cancer cells. The prospects of several peptides and their mechanisms of action have received significant attention. BF-30, a 30 amino acid residue peptide isolated from the venom of the snake, Bungarus fasciatus, is reported to have antibacterial and antitumor activities...
November 14, 2018: Peptides
Katarzyna Ciaćma, Jerzy Więckiewicz, Sylwia Kędracka-Krok, Magdalena Kurtyka, Małgorzata Stec, Maciej Siedlar, Jarek Baran
BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively eliminates tumor cells. However, the short biological half-life of this molecule limits its potential use in the clinic. Our aim was to construct a recombinant strain of nonpathogenic Lactococcus lactis bacteria as a vector for effective and prolonged human TRAIL production. Herein, we examined the expression and secretion conditions leading to the production of biologically active protein in vitro...
November 16, 2018: Microbial Cell Factories
Qi Luo, Guangyu Wei, Xiaoqing Wu, Kai Tang, Mengdi Xu, Yulu Wu, Yun Liu, Xiaoqian Li, Zengtian Sun, Wen Ju, Kunming Qi, Chong Chen, Zhiling Yan, Hai Cheng, Feng Zhu, Zhenyu Li, Lingyu Zeng, Kailin Xu, Jianlin Qiao
BACKGROUND: Platycodin D (PD) is one of the major bioactive components of the roots of Platycodon grandiflorum and possesses multiple biological and pharmacological properties, such as antiviral, anti-inflammatory, and anti-cancer activities. However, whether it affects platelet function remains unclear. This study aims to evaluate the role of PD in platelet function and thrombus formation. METHODS: Platelets were treated with PD followed by measuring platelet aggregation, activation, spreading, clot retraction, expression of glycoprotein receptors...
November 15, 2018: Journal of Translational Medicine
Eduardo Hernández-Vázquez, Alejandra Chávez-Riveros, Antonio Nieto-Camacho, Luis D Miranda
Inflammation is widely reported as a main factor for the development of chronic diseases such as cancer, diabetes and even metabolic syndrome. Thus, the search for novel anti-inflammatory compounds is required. Herein, we describe the synthesis of a collection of peptidic pyrazinones by a convenient approach which involved a multicomponent isocyanide-based reaction followed by a tandem deprotection/oxidative cyclization step. The series was tested for its potential anti-inflammatory capacity in an in vivo murine model, where 4 compounds were identified that inhibited tetradecanoylphorbol acetate-induced (TPA) edema more than 75%...
November 14, 2018: ChemMedChem
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