The C-terminal sequences of porcine thrombin are active as antimicrobial peptides

Abstract

The C-terminal sequences of porcine thrombin encode a series of peptides with the characteristics of net positive charge and hydrophobicity, suggesting antimicrobial potential. In this study, we synthesized truncated C-terminal peptides to explore their antimicrobial potency and structure-activity relationship. The results showed that some peptides exerted antimicrobial activity against Gram-positive and Gram-negative bacteria, with selectivity for microbial membranes. The antimicrobial potency of the peptides increased with the extension of chain length. Considering toxicity to red blood cells, the 21-mer peptide T-6 displayed the highest therapeutic index of 43.4, suggesting its higher cell selectivity. Typical α-helical conformations were observed upon binding to a bacteria-mimicking environment. The derivatives tended to interact preferentially with negatively charged vesicles compared to zwitterionic vesicles. Flow cytometry and electron microscopy revealed that the peptides targeted bacterial cell membranes and disrupted cytoplasmic membrane integrity, thereby causing the release of cellular contents leading to cell death. Peptide-membrane interaction experiments provided evidence that the peptides killed bacteria via a membrane-mediating mechanism. In summary, the C-terminal sequence of porcine thrombin has antimicrobial functions.

This article is protected by copyright. All rights reserved.

A series of short antimicrobial peptides were obtained from C-terminus of porcine thrombin to investigate their antimicrobial potency, structure-activity relationship and mechanism. The 21-residue peptide T-6 exhibited a considerably higher level of cell selectivity with TI of 43.4. T-6 demonstrated a typical α-helix structure in membrane-mimetic environment and rapidly disrupted the microbial membrane, leading to leakage of the intracellular content and eventual cell death at its MIC.

from Therapeutics via xlomafota13 on Inoreader http://ift.tt/2aiBAQO

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2a2ebkP
via IFTTT