Recent studies have shown that antimicrobial peptides (AMPs) can self-assemble into supramolecular structures, but this has been overlooked as causative of their antimicrobial activity. Also, the higher antimicrobial potency of d-enantiomers compared to l-enantiomers of AMPs cannot always be attributed to their different resistance to protease degradation. Here, we tested all l- and d-amino acid versions of GL13K, an AMP derived from a human protein, to study structural links between the AMP secondary structure, supramolecular self-assembly dynamics, and antimicrobial activity. pH dependence and the evolution of secondary structures were related to a self-assembly process with differences among these AMPs. The two GL13K enantiomers formed analogous self-assembled twisted nanoribbon structures, but d-GL13K initiated self-assembly faster and had notably higher antimicrobial potency than l-GL13K. A non-antimicrobial scrambled amino acid version of l-GL13K assembled at a much higher pH to form distinctively different self-assembled structures than l-GL13K. Our results support a functional relationship between the AMP self-assembly and their antimicrobial activity.
Bibliographical noteFunding Information:
The authors acknowledge Dr Wei Zhang and Dr Bob Hafner, Characterization Facilities, University of Minnesota (UMN) for technical assistance with TEM imaging. The authors also acknowledge Dr James Marti, Minnesota Nano Center, UMN for technical assistance with titration curve assessment; Nicholas Fischer, MDRCBB, UMN for technical assistance with the fluorescence microplate reader; and Ms Ruoqiong Chen, School of Dentistry, UMN for technical assistance with MIC analysis. The authors also acknowledge Professor Sven Gorr, School of Dentistry, UMN for constructive discussions regarding the effect of proteases on the activity of L-and D-GL13K peptides and for donating the S. gordonii strain used here. The authors acknowledge Erik Skoe for language editing of the manuscript. This research study was supported by the National Institute for Dental and Craniofacial Research of the National Institutes of Health [grant number RO1DE026117 to C. A.]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. S. A. acknowledges financial support from the Ministry of Economy, Industry and Competitiveness of the Spanish Government through a travel fellowship for graduate students [Ref. ID: EEBB-I-18-13053]. The funding bodies had no role in study design, the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the article for publication. Parts of this work were carried out in the University of Minnesota I.T. Characterization Facility, which receives partial support from NSF through the MRSEC program. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nano Coordinated Infrastructure Network (NNCI) under Award Number ECCS-1542202.
© The Royal Society of Chemistry.