Peptídeos modificados derivados da crotalicidina e crotamina do veneno de cascavel e do cnidário marinho: atividades farmacológicas recentes

Abstract

Biotecnology plays an important role in the discovery of new and promising pharmacological targets, allowing for the identification of bioactive peptides. Venom peptides have gained prominence in recent years due to their selectivity and ability to target specific receptors. This thesis covers two distinct research focuses in which peptides derived from the venom of a marine cnidarian and a rattlesnake were investigated for their applications in embryo technology and ion channel neurophysiology. The first part of the thesis assessed the potential of synthetic peptides derived from the transcriptome of a cnidarian (Chi, PPA, SSB) and snake venom peptide analogs (SFR-Ctn[1-9], SFR-Ctn[16-24], and NRTP1) concerning their activities on ion channels, cytoprotection, and electrophysiological patterns. The objective was to investigate the modulation of peptides on ion channels and their cyto - and neuroprotective roles. Through electrophysiological techniques and in vitro cytotoxicity reversal or prevention, the peptides exhibited a significant ability to block ion channels, particularly sodium and calcium ion channels, supported by in silico molecular docking analyses. Additionally, cytoprotective and antioxidant properties were observed in neuroblast and neuroendocrine cells. The second part focused on investigating parthenogenetic activation using the peptide derived from crotalicidin, RhoB-Ctn[1-9]. The aim was to evaluate the potential of this modified peptide to induce in vitro parthenogenesis and activate bovine embryos. The results revealed that the RhoB-Ctn[1-9] peptide has the ability to induce parthenogenesis, cleavage, and blastocyst formation efficiently. Using Lightsheet fluorescence microscopy, the peptides' ability to penetrate the zona pellucida, internalize, and accumulate in the cytoplasm of dividing cells was visualized, confirming the in silico data via molecular docking. It was found that structurally modified venom peptides can not only have direct therapeutic actions but also act as adjunct components in various areas such as in vitro fertilization and neurophysiological modulation. These findings provide important examples and insights for biotechnology, with promising implications for future therapeutic applications and the development of innovative strategies for molecular and cellular studies.