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      Drug Design, Development and Therapy (submit here)

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      Sugar Codes Conjugated Alginate: An Innovative Platform to Make a Strategic Breakthrough in Simultaneous Prophylaxis of GERD and Helicobacter pylori Infection

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          Abstract

          Introduction

          Currently, gastroesophageal reflux disease (GERD) is one of the most ubiquitous problems in clinical practice. An antacid-alginate combination (under the trade name Gaviscon) is a natural-based product that effectively suppresses GERD. This product acts via the formation of viscous gel that floats on the top of the gastric content. On the other hand, efficient management of Helicobacter pylori infection with minimal side effects is an important goal for gastroenterologists. Furthermore, some H. pylori-positive patients suffer from GERD.

          Methods

          Here, we present the results of investigations on alginate conjugated to sugar codes in order to find initial clues regarding the potential ability of this conjugate in the simultaneous prophylaxis of GERD and H. pylori infection in an in vitro assay.

          Results

          It is noteworthy that our results reveal that sugar codes conjugated alginate considerably decrease (approximately 74%) the adhesion of H. pylori to gastric epithelial cells in vitro. Moreover, surprisingly after conjugation of sugar codes, alginate can maintain its ability to create gel. Our results demonstrate that alginate conjugated to sugar codes is not cytotoxic.

          Conclusion

          The preparation of these conjugates can be regarded as the first step to establish a new roadmap for the simultaneous prevention of GERD and H. pylori infection in future studies on in vivo models.

          Most cited references26

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          Roles of galectins in infection.

          Galectins, which were first characterized in the mid-1970s, were assigned a role in the recognition of endogenous ('self') carbohydrate ligands in embryogenesis, development and immune regulation. Recently, however, galectins have been shown to bind glycans on the surface of potentially pathogenic microorganisms, and function as recognition and effector factors in innate immunity. Some parasites subvert the recognition roles of the vector or host galectins to ensure successful attachment or invasion. This Review discusses the role of galectins in microbial infection, with particular emphasis on adaptations of pathogens to evasion or subversion of host galectin-mediated immune responses.
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            A streptavidin variant with slower biotin dissociation and increased mechanostability

            Streptavidin binds biotin-conjugates with exceptional stability, but dissociation does occur and can be limiting in imaging, DNA amplification, and nanotechnology. We identified a mutant streptavidin, which we call traptavidin, showing ~10-fold slower biotin off-rate, increased mechanical strength, and improved thermostability; this resilience should find diverse applications. We show that the motor protein FtsK could strip proteins from DNA, rapidly displacing streptavidin from biotinylated DNA; traptavidin resisted displacement and thus indicated the force generated by FtsK translocation.
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              Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence

              The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                DDDT
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                17 June 2020
                2020
                : 14
                : 2405-2412
                Affiliations
                [1 ]Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran, Iran
                [2 ]Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                [3 ]Peptide Chemistry Research Center, K. N. Toosi University of Technology , Tehran, Iran
                [4 ]Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                [5 ]Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine , Isehara, Kanagawa 259-1193, Japan
                [6 ]Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University , Heidelberg, Germany
                Author notes
                Correspondence: Ismaeil Haririan Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran, Iran Email haririan@tums.ac.ir
                Author information
                http://orcid.org/0000-0002-2135-7581
                http://orcid.org/0000-0002-8994-6163
                Article
                255611
                10.2147/DDDT.S255611
                7306573
                1dd3a6af-2d2e-4624-a2e1-0750d09a648a
                © 2020 Moayedi et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 26 March 2020
                : 10 June 2020
                Page count
                Figures: 6, References: 36, Pages: 8
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                gerd,helicobacter pylori infection,sugar codes,alginate,conjugation

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