Short Photoswitchable Antibacterial Peptides

• Published in: ChemMedChem Vol. 15; no. 16; pp. 1505 - 1508
• Main Authors: Yeoh, Yuan Qi, Horsley, John R., Yu, Jingxian, Polyak, Steven W., Jovcevski, Blagojce, Abell, Andrew D.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 19.08.2020; Wiley Subscription Services, Inc
• Subjects: amphiphilicity; Antibacterial activity; antibacterial peptides; Antibiotics; Azo compounds; azobenzene photoswitch; Chains; Chemistry, Medicinal; Hydrophobicity; Life Sciences & Biomedicine; Lipids; Minimum inhibitory concentration; Peptides; Pharmacology & Pharmacy; Protein structure; Science & Technology; Secondary structure; Staphylococcus aureus; UV; hydrophobicity; PHOTOISOMERIZATION; antibacterial peptides; AZOBENZENE; amphiphilicity; ANTIMICROBIAL PEPTIDES; azobenzene photoswitch; Staphylococcus aureus
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.202000280

Three photoswitchable tetrapeptides, based on a known synthetic antibacterial, were designed and synthesized to determine activity against Staphylococcus aureus. Each peptide contains an azobenzene photoswitch incorporated into either the N‐terminal side chain (1), C‐terminal side chain (2), or the C‐terminus (3) to allow reversible switching between cis‐ and trans‐enriched photostationary states. Biological assays revealed that the C‐terminus azobenzene (3) possessed the most potent antibacterial activity, with an MIC of 1 μg/mL. In this study, net positive charge, hydrophobicity, position of the azobenzene, secondary structure, and amphiphilicity were all found to contribute to antibacterial activity, with each of these factors likely facilitating the peptide to disrupt the negatively charged bacterial lipid membrane. Hence, these short photoswitchable antibacterial tetrapeptides provide insights for the future design and synthesis of antibiotics targeting S. aureus. Potent potential: Three short peptides with an azobenzene photoswitch incorporated either on a side chain or the C‐terminus allow reversible switching between the cis‐ and trans‐enriched photostationary states. All trans‐enriched states were more potent against S. aureus than their cis‐enriched counterparts, with the peptide modified at the C‐terminus exhibiting the greatest antibacterial activity (MIC=1 μg/mL).