Different Biological Activities of Histidine-Rich Peptides Are Favored by Variations in Their Design.

Morane Lointier,Elise Glattard,Antoine Kichler,Candice Dussouillez,Burkhard Bechinger

doi:10.3390/toxins13050363

Abstract

The protein transduction and antimicrobial activities of histidine-rich designer peptides were investigated as a function of their sequence and compared to gene transfection, lentivirus transduction and calcein release activities. In membrane environments, the peptides adopt helical conformations where the positioning of the histidine side chains defines a hydrophilic angle when viewed as helical wheel. The transfection of DNA correlates with calcein release in biophysical experiments, being best for small hydrophilic angles supporting a model where lysis of the endosomal membrane is the limiting factor. In contrast, antimicrobial activities show an inverse correlation suggesting that other interactions and mechanisms dominate within the bacterial system. Furthermore, other derivatives control the lentiviral transduction enhancement or the transport of proteins into the cells. Here, we tested the transport into human cell lines of luciferase (63 kDa) and the ribosome-inactivating toxin saporin (30 kDa). Notably, depending on the protein, different peptide sequences are required for the best results, suggesting that the interactions are manifold and complex. As such, designed LAH4 peptides assure a large panel of biological and biophysical activities whereby the optimal result can be tuned by the physico-chemical properties of the sequences.

Highlights

Peptides are natural polymers that act as hormones, are used for signaling or are part of defense mechanisms against bacterial, fungal or viral infections [1,2,3]
The amino acid modifications from the original LAH4 sequence result in hydrophilic angles ranging from 60◦ to 180◦ (Table 1 and Figure S1)
The results indicate that LAH4-derived peptides were able to deliver proteins of different molecular weight and different isoelectric points into cells

Summary

Introduction

Peptides are natural polymers that act as hormones, are used for signaling or are part of defense mechanisms against bacterial, fungal or viral infections [1,2,3]. There are many possible biomedical applications involving peptides or the mimetics thereof. Peptides and their building blocks are biodegradable, they can be produced in a reproducible and scalable manner, and procedures assuring analytical control of the products and their quality are well established. Molecules have been created that represent the physico-chemical properties of known peptides [4,5,6,7]

Methods

Results

Conclusion