"Selective O-glycosylation of the neurovespin(tyr) peptide: assessment of its toxicity and therapeutic potential in an acute seizure model.”
“Epilepsy; Glycosylation; Antiepileptic drugs; Electroencephalography; Toxicity."
“Epilepsy is one of the major chronic neurological disorders, affecting approximately 50 million people worldwide. It is characterized by a reduced threshold for excitation in neuronal circuits, with epileptic seizures resulting from abnormal synchronous neuronal discharges. Despite the availability of several antiepileptic drugs, many cause significant side effects or fail to effectively control seizures, highlighting the need for new treatments. In this context, a bioinspired peptide derived from the venom of the wasp Polybia occidentalis, named neurovespin, was developed and demonstrated protection against chemically induced seizures in mice. Currently, neurovespin is undergoing registration for use in dogs and cats with refractory epilepsy and has been licensed to the biotechnology company Biointech. Despite its antiepileptic efficacy, neurovespin has a short half-life, requiring frequent administration. Studies suggest that peptide glycosylation, particularly tyr-O-glycosylation, can significantly improve peptide stability and biological activity. To enable this modification, neurovespin was structurally altered with the addition of a tyrosine residue, resulting in neurovespin(tyr). This project aimed to glycosylate neurovespin(tyr) and evaluate its neuroprotective effect in an acute seizure model induced by pentylenetetrazol (PTZ) in mice, complemented by behavioral and electroencephalographic (video-EEG) analyses. Furthermore, the acute in vivo toxicity of the neurovespin, neurovespin(tyr), and neurovespin(gly) variants was assessed. To achieve this, the glycosylated peptide was synthesized, purified, and characterized using reverse-phase liquid chromatography (HPLC) and mass spectrometry (MS). Subsequently, toxicity and neuroprotective effect assays were conducted in animal models, providing a comprehensive analysis of the therapeutic potential of modified neurovespin.”