Short-Chained Linear Scorpion Peptides: A Pool for Novel Antimicrobials

Abstract

Scorpion venom peptides are generally classified into two main groups: the disulfide bridged peptides (DBPs), which usually target membrane-associated ion channels, and the non-disulfide bridged peptides (NDBPs), a smaller group with multifunctional properties. In the past decade, these peptides have gained interest because most of them display functions that include antimicrobial, anticancer, haemolytic, and anti-inflammatory activities. Our current study focuses on the short (9-19 amino acids) antimicrobial linear scorpion peptides. Most of these peptides display a net positive charge of 1 or 2, an isoelectric point at pH 9-10, a broad range of hydrophobicity, and a Grand Average of Hydropathy (GRAVY) Value ranging between -0.05 and 1.7. These features allow these peptides to be attracted toward the negatively charged phospholipid head groups of the lipid membranes of target cells, a force driven by electrostatic interactions. This review outlines the antimicrobial potential of short-chained linear scorpion venom peptides. Additionally, short linear scorpion peptides are in general more attractive for large-scale synthesis from a manufacturing point of view. The structural and functional diversity of these peptides represents a good starting point for the development of new peptide-based therapeutics.

Keywords: AMPs; antimicrobials; scorpion venom; therapeutics; venom peptides.

Figure 2

Selected conformations of the peptide fragments GIKSLF (left) and GKLWEG (right) obtained with PEP-FOLD 4.0 [66]. Hexapeptide GKLWEG is common in peptides pantinin-1 (NDBP-4.20), StCT1 (NDBP-4.8), StCT2 (NDBP-4.15), UyCT1 (NDBP-4.16), and UyCT2 (NDBP-4.17). Hexapeptide GIKSLF is common in the C-terminal region of six peptides, IsCT, IsCT2, UyCT3, HP1090, Um4, and Um2.

Figure 1

Percentages of Staphylococcus aureus invasive isolates resistant to methicillin (MRSA), by country, EU/EEA, 2022 [3]. The figure shows the percentage of Staphylococcus aureus invasive isolates resistant to methicillin (MRSA) compared to the total number of Staphylococcus aureus isolates across countries in the EU/EEA. Values in southern and south-eastern countries are generally higher than in northern countries. For example, the MRSA isolates accounted for up to 5% in Sweden and up to 50% in Cyprus.