Self-assembly dynamics and antimicrobial activity of all l- and d-amino acid enantiomers of a designer peptide

Abstract

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 AMPs secondary structure, supramolecular self-assembly dynamics, and antimicrobial activity. pH dependence and the evolution of secondary structures were related to a self-assembling 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 LGL13K assembled at a much higher pH to form distinctively different self-assembled structures than L-GL13K. Our results support a functional relationship between the AMPs self-assembly and their antimicrobial activity.

The Human LL-37(17-29) Antimicrobial Peptide Reveals a Functional Supramolecular Nanostructure

“…The higher the indicated percentage, the more buried the residue is on an isolated helix by surrounding helices within the four-helix bundle. 2 The number indicated is the percentage of the SASA per residue on an isolated helix versus the SASA of this residue within the fibrillar assembly, averaged for the two chains. The higher the indicated percentage, the more buried the residue is on an isolated helix by surrounding helices within the fibrillar assembly.…”

“…Antimicrobial peptides (AMPs) are canonical components of the innate immune system of many organisms (1). AMP self-assembly bears functional relevance and can enhance antimicrobial activity (2). Certain AMPs assemble into well-ordered fibrils that resemble amyloids (3)(4)(5)(6)(7)(8), which are proteins known to form cross- fibrils composed of tightly mated β-sheets, and have been associated with neurodegenerative and systemic diseases (9,10).…”

Targeting the oral plaque microbiome with immobilized anti-biofilm peptides at tooth-restoration interfaces

“…The high resistance of the non-native D-peptides to proteases-induced digestion and degradation might be responsible for their robust performance [16,45]. We have also recently demonstrated that the differences between D-and L-peptides in the dynamics of peptide structural arrangement/ assembly is correlated with their antimicrobial potency [46]. Understanding of the impact of these AAMPs on different commensal and pathogenic bacteria is crucial for potential applicability, thus we further study the bacterial selectivity of our AAMPs coatings.…”

Characteristic of AMP and the effects of chemical modifications on the modulation of their antimicrobial properties

“…Minimal Inhibitory Concentration) pokazały, że D-GL13K wykazywał znacznie większą aktywność względem bakterii Gram-dodatnich (Enterococcus faecalis, Streptococcus gordonii) [45,46]. Z kolei Oliva ze współpracownikami w swojej pracy badawczej skupili się na syntezie trzech peptydów: P9NaI(SS), P9Trp(SS) i P9NaI(SR) (Ryc.…”