Design of novel analogues of short antimicrobial peptide anoplin with improved antimicrobial activity

Abstract

Currently, novel antibiotics are urgently required to combat the emergence of drug-resistant bacteria. Antimicrobial peptides with membrane-lytic mechanism of action have attracted considerable interest. Anoplin, a natural α-helical amphiphilic antimicrobial peptide, is an ideal research template because of its short sequence. In this study, we designed and synthesized a group of analogues of anoplin. Among these analogues, anoplin-4 composed of D-amino acids displayed the highest antimicrobial activity due to increased charge, hydrophobicity and amphiphilicity. Gratifyingly, anoplin-4 showed low toxicity to host cells, indicating high bacterial selectivity. Furthermore, the mortality rate of mice infected with Escherichia coli was significantly reduced by anoplin-4 treatment relative to anoplin. In conclusion, anoplin-4 is a novel anoplin analogue with high antimicrobial activity and enzymatic stability, which may represent a potent agent for the treatment of infection.

Recombinant Expression of a Modified Shrimp Anti-Lipopolysaccharide Factor Gene in Pichia pastoris GS115 and Its Characteristic Analysis

“…This is very similar to that of the reported ALF isoforms without any modification [39] and other AMPs [40]. Different from the traditional antibiotics, which have specific molecular targets, mFcALF2 might function by binding to the cell membrane of the bacteria through physical process, which is similar to that for other AMPs [41]. mFcALF2 showed some typical characteristic of AMPs.…”

Isolation, functional characterization, and biological properties of MCh‐AMP1, a novel antifungal peptide from Matricaria chamomilla L.

“…Hydrophobicity is one of the important parameters for the antimicrobial activity of AMPs which facilitates the interaction between AMPs and cell membranes (Chen et al, 2007;Kim, Jang, Kim, & Cho, 2013). The positive net charge residues of the AMPs promoted their electrostatic attraction toward anionic phospholipids in fungal membranes (Van Der Weerden, Bleackley, & Anderson, 2013;Wang et al, 2014). Boman index provides an estimation of potential AMPs for binding to other proteins where the index value of ≤1 can be indicative of higher antimicrobial activity of AMPs with few side-effects (Boman, 2003).…”

Disulfide engineering on temporin‐SHf: Stabilizing the bioactive conformation of an ultra‐short antimicrobial peptide

“…SAMPs are prone to denaturation under harsh conditions/chemical modifications and susceptible for proteolytic degradation which may leads to the loss of antimicrobial activity (Bessalle et al, 1993;Hilpert, Volkmer-Engert, Walter, & Hancock, 2005;Mangoni, 2006;Mangoni, Grazia, Cappiello, Casciaro, & Luca, 2016;Nguyen, Haney, & Vogel, 2011). Different strategies have been adopted to improve the stability of short antimicrobial peptides such as capping of N-and C-terminus of the peptide (Albada et al, 2012;Munk et al, 2013), incorporation of unnatural/D-configured amino acid (Albada et al, 2012;Haug, Stensen, Stiberg, & Svendsen, 2004;Wang et al, 2014), and backbone cyclization of the peptide (Fjell, Hiss, Hancock, & Schneider, 2011;Nguyen et al, 2010;Ramesh et al, 2016). Evolutionarily adopted strategy to improve the stability of bioactive conformations of short linear peptide motifs is through incorporation of cysteine disulfide.…”