Synthesis and antibacterial activity of trivalent ultrashort Arg-Trp-based antimicrobial peptides (AMPs)Electronic supplementary information (ESI) available: Experimental procedures (preparation of new compounds) and characterizing data. See DOI: 10.1039/c4md00327f

• Main Authors: Hoffknecht, Barbara C, Albada, H. Bauke, Sturm, Marina, Prochnow, Pascal, Bandow, Julia E, Metzler-Nolte, Nils
• Format: Article
• Language: English
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c4md00327f

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. Multivalent display of identical ultrashort (only 2-3 amino acids long) antimicrobial peptides (AMPs) was used in order to create potential new antimicrobial agents.