Solid-Phase Synthesis and Antibacterial Activity of an Artificial Cyclic Peptide Containing Two Disulfide Bridges

Abstract

Synthesis of artificial antibacterial peptides containing multiple disulfide bridges is of particular interest in bioorganic chemistry. In this paper, a straightforward on-resin synthesis of a cyclic peptide containing two disulfide bridges by orthogonal protection approach is presented. This artificial peptide is a biomimetic peptide that has structural combination of Magainin and Defensins peptides at the same time. It showed antibacterial activity against a number of Gram-negative and Gram-positive bacteria including Pseudomonas aeruginosa, Proteus mirabilis, Escherichia coli, Staphylococcus aureus, and others with MICs between 10 and 35 µg/mL. In general, Gram-negative bacteria showed more susceptibility to this artificial peptide than Gram-positive bacteria.