Development of peptide/guanidine bioconjugate GVL-2-MAP-3 with antimicrobial activity.

• Grant number: 25/04988-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Eduardo Maffud Cilli
• Grantee: Gabriel Antunes Santoro
• Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Leishmaniasis and many other infirmities, such as parasitarian, bacterial and viral infections embody the field of infectious diseases, of which many are at its highest infection rate as of now, having leishmaniasis - a tropical, neglected parasitical disease caused by the bite of the female infected phlebotomine sand flies (Diptera: Psychodidae)- affecting more than a million people annually worldwide, as stated by WHO, with its only treatment being the continuous and numerous applications of amphotericin B injections, a compound of high cytotoxicity. Although of extreme concern, leishmaniasis are not the only alarming issue: bacterial and viral infections are becoming more common - and deadly - each year, thanks to new mutations and strains becoming resistant to common medicine. Viruses, such as chikungunya, are also extremely present and fatal, mainly in tropical, less fortunate regions, therefore the lack of research and interest for the development of new molecules. Enlightened by the aforementioned, it's clear that new drugs and compounds must be studied for its antimicrobial capabilities, such as the antimicrobial peptides (AMP), naturally occurring molecules made up of a short chain of amino acids. The objective of this work is to synthesize, bioconjugate, characterize and perform in vitro assays with the temporin-derived AMP MAP-3, of structure NH2-LLKKVLALLKKVL-COOH (which's activity is already described), when bonded to a guanidine moiety of name GVL-2, in hopes of achieving better performance against the pathogens above mentioned, through the usage of circular dichroism, anti-Leishmania assays, antiviral assays on Oropouche orthobunyavirus and antibacterial assays on ESKAPE lineages.