A polyalanine peptide derived from polar fish with anti-infectious activities

Abstract

Due to the growing concern about antibiotic-resistant microbial infections, increasing support has been given to new drug discovery programs. A promising alternative to counter bacterial infections includes the antimicrobial peptides (AMPs), which have emerged as model molecules for rational design strategies. Here we focused on the study of Pa-MAP 1.9, a rationally designed AMP derived from the polar fish Pleuronectes americanus. Pa-MAP 1.9 was active against Gram-negative planktonic bacteria and biofilms, without being cytotoxic to mammalian cells. By using AFM, leakage assays, CD spectroscopy and in silico tools, we found that Pa-MAP 1.9 may be acting both on intracellular targets and on the bacterial surface, also being more efficient at interacting with anionic LUVs mimicking Gram-negative bacterial surface, where this peptide adopts α-helical conformations, than cholesterol-enriched LUVs mimicking mammalian cells. Thus, as bacteria present varied physiological features that favor antibiotic-resistance, Pa-MAP 1.9 could be a promising candidate in the development of tools against infections caused by pathogenic bacteria.

In silico optimization of a guava antimicrobial peptide enables combinatorial exploration for peptide design

“…The peptide guavanin 2 was synthesized by stepwise solid phase using the N -9-fluorenylmethyloxycarbonyl (FMOC) strategy and purified by high-performance liquid chromatography, with purity >95% by Peptide 2.0 (Virginia, USA). The sequence and degree of purity (>95%) was confirmed by MALDI-ToF analyses 13 .…”

“…However, both strategies are strongly influenced by the information encoded in AMP sequences deposited in databases, which limits their capacity to identify unknown AMP sequences beyond those described in the literature. In cerebro design methods rely on the bacterial membrane as a target for AMPs; in practical terms, this kind of design approach creates and/or modifies peptide sequences by means of increasing peptide cationicity and hydrophobicity, mainly by inserting lysine, leucine, and alanine residues within the sequence, thus enhancing the interaction between peptide and membrane 12 , 13 . Computer-aided design methods make it possible to explore the peptide sequence space of AMPs using a number of algorithms.…”

Anti-Biofilm Activity of a Self-Aggregating Peptide against Streptococcus mutans

“…Synthetic peptides represent a promising class of anti-biofilm molecules, with activity against a variety of pathogens (Di Luca et al, 2015; Cardoso et al, 2016; de la Fuente-Núñez et al, 2016; Pletzer and Hancock, 2016). A cationic synthetic peptide, called P1, derived from the I xodes tick a nti f reeze g lyco p rotein (IAFGP), demonstrates potent anti-biofilm activity against Staphylococcus aureus , and confers an antivirulence effect in a catheter infection mouse model (Heisig et al, 2014).…”

Marine Antimicrobial Peptides: Nature Provides Templates for the Design of Novel Compounds against Pathogenic Bacteria

“…Cardoso et al [ 97 ] designed a novel polyalanine-rich cationic peptide, named Pa-MAP 1.9, which was rationally designed based on the HPLC-8 peptide derived from the polar fish Pleuronectes americanus . They proved that the peptide is a valuable candidate for the treatment of gram-negative bacterial infections especially in their biofilm state; moreover, it is not chemolytic and cytotoxic against mammalian cells.…”