Synthesis and antibacterial activity of trivalent ultrashort Arg-Trp-based antimicrobial peptides (AMPs)

Multivalent display of identical ultrashort (only 2–3 amino acids long) antimicrobial peptides (AMPs) was used in order to create potential new antimicrobial agents. A series of small synthetic arginine and tryptophan containing peptides was synthesized and covalently bound to two different trivalen...

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Bibliographic Details
Published in:MedChemComm 2015-02, Vol.6 (2), p.372-376
Main Authors: Hoffknecht, Barbara C., Albada, H. Bauke, Sturm, Marina, Prochnow, Pascal, Bandow, Julia E., Metzler-Nolte, Nils
Format: Article
Language:English
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Summary:Multivalent display of identical ultrashort (only 2–3 amino acids long) antimicrobial peptides (AMPs) was used in order to create potential new antimicrobial agents. A series of small synthetic arginine and tryptophan containing peptides was synthesized and covalently bound to two different trivalent scaffold molecules using the copper( i )-catalyzed alkyne–azide cycloaddition (CuAAC) reaction. The effect of steric preorganization of AMPs on the antibacterial activity was studied using a 1,3,5-tris(azidomethyl)benzene and a 1,3,5-tris(azidomethyl)-2,4,6-triethylbenzene substituted scaffold. The comparison of these two scaffolds showed that preorganisation leads to at least twice as active compounds. We furthermore obtained a synergistic effect and could show that the presence of a certain number of amino acids in close proximity is more important than their relative spatial orientation.
ISSN:2040-2503
2040-2511
DOI:10.1039/C4MD00327F