Retro analog concept: comparative study on physico-chemical and biological properties of selected antimicrobial peptides

Abstract

Increasing drug resistance of common pathogens urgently needs discovery of new effective molecules. Antimicrobial peptides are believed to be one of the possible solutions of this problem. One of the approaches for improvement of biological properties is reversion of the sequence (retro analog concept). This research is based on investigation of antimicrobial activity against Gram-positive, Gram-negative bacteria, and fungi, hemolysis of erythrocytes, interpretation of the circular dichroism spectra, measurement of counter-ion content, and assessment of the peptide hydrophobicity and self-assembly using reversed-phase chromatography. The experiments were conducted using the following peptides: aurein 1.2, CAMEL, citropin 1.1, omiganan, pexiganan, temporin A, and their retro analogs. Among the compounds studied, only retro omiganan showed an enhanced antimicrobial and a slightly increased hemolytic activity as compared to parent molecule. Moreover, retro pexiganan exhibited high activity towards Klebsiella pneumoniae, whereas pexiganan was in general more or equally active against the rest of tested microorganisms. Furthermore, the determined activity was closely related to the peptide hydrophobicity. In general, the reduced hemolytic activity correlates with lower antimicrobial activity. The tendency to self-association and helicity fraction in SDS seems to be correlated. The normalized RP-HPLC—temperature profiles of citropin 1.1 and aurein 1.2, revealed an enhanced tendency to self-association than that of their retro analogs.

Antimicrobial Activity of Selected Antimicrobial Peptides Against Planktonic Culture and Biofilm of Acinetobacter baumannii

“…At the same time, omiganan is less cytotoxic than its retro counterpart owing to the lower rate of hemolysis. [ 53 ]. Temporin A was the weakest peptide tested in our study and the most cytotoxic one.…”

Antimicrobial activity of a porphyrin binding peptide

“…Previously, our group reported the development of peptide based scaffolds for the binding and orientation of an anionic porphyrin, meso‐tetra(4‐sulfonatophenyl)porphyrin (), into an excitonically coupled J‐aggregate structure . This peptide scaffold was originally synthesized based on the amphiphilic AMP ISM‐78 also referred to as r‐pexiganan . This peptide was shown to promote J‐aggregate formation over a wider range of pH values than previously reported …”

A Novel Delivery System for the Controlled Release~of Antimicrobial Peptides: Citropin 1.1 and Temporin A

“…From the therapeutic point of view, it is very important to achieve therapeutic concentration of APIs in the target tissue. In the current work, we also investigated the daily release rate of AMPs after 1, 7, 14, 21, and 28 days ( Figure 5 ) considering their reported MIC and MHC values [ 13 , 31 ]. We focused on the anti-infectious effect of AMPs in infections caused by major pathogens in surgical wound infections, Staphylococcus aureus, Enterococcus faecalis , Escheria coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa [ 32 ].…”

“…In the case of TEMP, maximum concentration was reached after 14 days of incubation in PBS at pH 7.4 at 37 °C. Interestingly, the maximum CIT daily release concentration was reached after 7 and 21 days (about 280 µg·mL −1 ), and this value exceeded the MHC values (about 256 µg·mL −1 [ 31 ]). For PCL-2, the highest daily concentration of both peptides was noted after 21 days.…”