Investigating the effects of cyclisation on the structure and antimicrobial activity of β-boomerang and thanatin

Abstract

The increase in antimicrobial resistance is a serious global health crisis. Hence, research into antibiotic alternatives like antimicrobial peptides (AMPs) is vital to combat drug-resistant pathogens. This study aims to investigate the effects of cyclisation on the structure and antimicrobial activity of β-boomerang and thanatin, two AMPs with the potential to become potent antimicrobial drugs, via NMR spectroscopy and MIC assays. Thus, determining whether cyclisation increases the stability and antimicrobial activity of β-boomerang and whether cyclisation can replace the disulfide bond in thanatin. The study revealed that linear β-boomerang and cyclic thanatin were unstructured in free solution while cyclic β-boomerang had a β-sheet structure in free solution. Both linear and cyclic thanatin were found to have poor antimicrobial activity. On the other hand, both linear and cyclic β-boomerang have decent antimicrobial activity, but cyclic β-boomerang exhibited better antimicrobial activity than linear β-boomerang. Hence, one can conclude that cyclisation successfully increased the stability and antimicrobial activity of β-boomerang but failed to replace the disulfide bond in thanatin. The findings from this study will be useful in the development of AMPs to combat drug-resistant bacteria.