Solid-phase synthesis and antibiotic activities of cyclodecapeptides on the scaffold of naturally occurring Laterocidin

The development of new antibacterial therapeutic agents capable of halting microbial resistance is a chief pursuit in clinical medicine. Laterocidin and its analogues were synthesized for the first time by solid-phase synthesis method via linking of the carboxyl group on side chain of Aspartate to Rink resin with the protection of side chain α-carboxyl group of Aspartate by Dmab as a temporary α-COOH protecting group for the on-resin cyclization. Different configuration of N- and C-terminal was benefit to peptide cyclization. Laterocidin analogue 3 (Asp¹→Asn¹, Phe⁴→Tyr⁴ and d-Tyr⁶→d-Phe⁶) demonstrated potent and broad antimicrobial properties, especially exhibited activity against clinical Methicillin-resistant Staphylococcus aureus (L-MRSA) and the gram-negative extended-spectrum β-lactamases-producing Escherichia coli (ESBLs E. coli) and L-E.coli. This finding has important significance to exploit new antibiotic medicine.