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    ksoren@stanford.edu
    University - Staff Department: Bioengineering Position: Life Science Research Professional 2

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  • Mail Code: 4245

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  • Halogenation as a tool to tune antimicrobial activity of peptoids. Scientific reports Molchanova, N. n., Nielsen, J. E., Sørensen, K. B., Prabhala, B. K., Hansen, P. R., Lund, R. n., Barron, A. E., Jenssen, H. n. 2020; 10 (1): 14805

    Abstract

    Antimicrobial peptides have attracted considerable interest as potential new class of antibiotics against multi-drug resistant bacteria. However, their therapeutic potential is limited, in part due to susceptibility towards enzymatic degradation and low bioavailability. Peptoids (oligomers of N-substituted glycines) demonstrate proteolytic stability and better bioavailability than corresponding peptides while in many cases retaining antibacterial activity. In this study, we synthesized a library of 36 peptoids containing fluorine, chlorine, bromine and iodine atoms, which vary by length and level of halogen substitution in position 4 of the phenyl rings. As we observed a clear correlation between halogenation of an inactive model peptoid and its increased antimicrobial activity, we designed chlorinated and brominated analogues of a known peptoid and its shorter counterpart. Short brominated analogues displayed up to 32-fold increase of the activity against S. aureus and 16- to 64-fold against E. coli and P. aeruginosa alongside reduced cytotoxicity. The biological effect of halogens seems to be linked to the relative hydrophobicity and self-assembly properties of the compounds. By small angle X-ray scattering (SAXS) we have demontrated how the self-assembled structures are dependent on the size of the halogen, degree of substitution and length of the peptoid, and correlated these features to their activity.

    View details for DOI 10.1038/s41598-020-71771-8

    View details for PubMedID 32908179