Seleção, Caracterização e Atividade Antibacteriana In Sílico de Peptídeos Inspirados na Osmotina de Calotropis Procera

Abstract

The decrease in antibiotic efficiency generates a great concern for individual and collective health, because these drugs are the main way to fight bacterial infections. Thus, it becomes essential the search for new antibacterial compounds that are effective and without toxicity to users. Antimicrobial peptides (AMPs) are part of a considerable group of molecules that can perform this task. That said, one way to begin studies with this material is from in silico research, which helps from peptide assembly to predictions of biological properties, toxicity, structure, and physicochemical characteristics. Knowing that the osmotin from Calotropis procera is a glycoprotein that already has its structure and amino acid

sequence studied, from it this work predicted four peptides (CpOsmPep-1, CpOsmPep-1a, CpOsmPep- 1b and CpOsmPep-1c) with size of ten amino acids and observed that, in addition to their

physicochemical characteristics similar to AMPs, they all showed antibiofilm and cell-penetrating properties, absence of toxicity and allergenicity, as well as stability in the human gastrointestinal environment. However, of the four peptides only one (CpOsmPep-1c) showed antimicrobial

characteristics. It was analyzed against molecular docking with the proteins UDP-N- acetylenolpyruvylglucosamine reductase from S. aureus, Tyrosyl-tRNA synthetase from S. aureus and

RbmA from V. cholera. Through this, it was observed that CpOsmPep-1c was shown to bind to target sites of all tested proteins, preventing it from performing its functions. The in silico ADMET profile of CpOsmPep-1c was also drawn and from this it was noted that the peptide tends to have a better cutaneous absorption, with a tendency to remain in blood vessels and be metabolized by cytochrome p450 via CYP3A4 and with a half-life of two hours. Furthermore, it was observed that the peptide showed no toxicity against kidneys, eyes, genes, and skin, however it was positive for hepatotoxicity and inhibited the hERG II protein, and may be cardiotoxic. Such results comprise the initial studies of a new peptide molecule that can be used in antibacterial treatments in the future, however, despite its remarkable biological characteristics, such molecule can still be improved for its best version to proceed to in vitro and in vivo studies.