Journal of Organic & Inorganic Chemistry

Management of H. pylori gastric infection via surface-grafted antimicrobial peptides

Annual Congress on Medicinal Chemistry, Pharmacology and toxicology
July 30 - 31 , 2018 Amsterdam , Netherlands

Paula Parreira, Claudia Monteiro, Vanessa Graca, Joana Gomes, Si�?­lvia Maia, Paula Gomes, Ines C Gonalves and M Cristina L Martins

i3S, Instituto de Investigacao e Inovacao em Saude, Universidade do Porto, Portugal INEB, Instituto de Engenharia Biomedica, Universidade do Porto, Portugal IPATIMUP, Instituto de Patologia e Imunologia Molecular, Universidade do Porto, Portugal LAQV-REQUIMTE, Departamento de Qu�?�?�?�?�?�?�?�?�?�?�?�?�?�?�?­mica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, Portugal FEUP, Faculdade de Engenharia, Universidade do Porto, Portugal Instituto de Ciencias Biomedicas Abel Salazar, Universidade do Porto, Portugal

Posters & Accepted Abstracts: J Org Inorg Chem

DOI: 10.21767/2472-1123-C3-009

Abstract

Helicobacter pylori chronic infection is associated, among other severe gastric disorders, with intestinal-type gastric carcinogenesis, being this the fifth most common cancer and the third leading cause of cancer-related death worldwide. Classical H. pylori eradication treatment, combining two antibiotics and a proton pump inhibitor, reduces the risk for gastric carcinoma development, but treatment of H. pylori infection is challenged by a dramatic fall in eradication rates all over the world. Currently, this bacterium is listed among the 16 antibiotic-resistant bacteria that pose greatest threat to human health according to the World Health Organization. Antimicrobial peptides (AMPs) present an alternative to conventional antibiotic therapies, being their most striking feature the low tendency to induce bacterial resistance, since AMPs selectively damage the bacterial membranes through mechanisms that bacteria find difficult to evade. In an in vivo scenario, “unbound AMPs” can undergo proteolysis and peptide aggregation, leading to efficiency decrease. AMP grafting onto nanoparticles has been reported as a good strategy to protect peptides from aggregation and enzymatic degradation in vivo, therefore increasing long-term stability and avoiding cytotoxicity is associated with application of high AMP concentrations. In this study, we demonstrated that the AMP MSI-78A could be surface-grafted without compromising its activity. Moreover, MSI-78A-decorated surfaces were highly effective against H. pylori, killing bacteria by contact in a short time span, since after 2 hrs only, 2% of H. pylori remained viable in suspension. These results encourage the utilization of grafted MSI-78A on biocompatible nanoparticles as an alternative to the currently available therapy against H. pylori, opening new routes for gastric infection management.