Abstract:

Ubiquicidin (UBI 1-59) is a cationic peptide of human origin which has shown to be antibacterial against a broad spectrum of pathogens, including methicillin resistant S. aureus (MRSA). The smaller synthetic fragment UBI 31–38 (RAKRRMQY) also exhibits strong activity against multi-drug resistant micro-organisms and offers a promising alternative for antimicrobial therapy and detection of infections in humans, as it is easy to be synthesized and produced under Good Manufacturing Practices. Although the basis of its antimicrobial activity is the interaction of the cationic domains of the peptide with the negatively charged surface of micro-organisms, the number of cationic residues itself cannot fully explain the antimicrobial activity of antimicrobial peptides. The physiological relevance, mechanism of action and antimicrobial spectrum of ubiquicidin are not well understood. The bioconjugation of peptides with pro-fluoropheres can be a good strategy to produce biologic probes. Coumarin derivatives have been investigated as pro-fluorophores since they are small in size, biocompatible, and easy to manipulate synthetically. Copper-catalyzed azide-alcine cycloaddition (CuAAC) reaction has been largely employed for bioconjugating fluorescent molecules to peptides under mild conditions and has applications in the field of cell biology and functional proteomics. We aimed to develop a synthetic route for the preparation of a fluorescent antimicrobial peptide UBI 31-38 to better identify cell interaction mechanisms and evaluate its intrinsic biological activity.