Halogenation as a tool to tune antimicrobial activity of peptoids
| Autor: | Paul R. Hansen, Natalia Molchanova, Annelise E. Barron, Bala K. Prabhala, Håvard Jenssen, Reidar Lund, Kristian Birk Sørensen, Josefine Eilsø Nielsen |
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| Rok vydání: | 2020 |
| Předmět: |
Staphylococcus aureus
Halogenation Cell Survival Antimicrobial peptides lcsh:Medicine chemistry.chemical_element Microbial Sensitivity Tests 010402 general chemistry Microbiology 01 natural sciences Article Cell Line chemistry.chemical_compound Peptoids Antibiotics Scattering Small Angle Chlorine Escherichia coli Humans lcsh:Science Multidisciplinary Antimicrobials 010405 organic chemistry Chemistry lcsh:R Peptoid Antimicrobial Chemical biology Combinatorial chemistry 0104 chemical sciences Bioavailability Anti-Bacterial Agents Halogen Pseudomonas aeruginosa lcsh:Q Peptides Antibacterial activity |
| Zdroj: | Scientific Reports Molchanova, N, Nielsen, J E, Sørensen, K B, Prabhala, B K, Hansen, P R, Lund, R, Barron, A E & Jenssen, H 2020, ' Halogenation as a tool to tune antimicrobial activity of peptoids ', Scientific Reports, vol. 10, no. 1, 14805 . https://doi.org/10.1038/s41598-020-71771-8 Molchanova, N, Nielsen, J E, Sørensen, K B, Prabhala, B K, Hansen, P R, Lund, R, Barron, A E & Jenssen, H 2020, ' Halogenation as a tool to tune antimicrobial activity of peptoids ', Scientific Reports, vol. 10, 14805 . https://doi.org/10.1038/s41598-020-71771-8 Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) 'Scientific Reports ', vol: 10, pages: 14805-1-14805-10 (2020) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-71771-8 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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