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.
Highlights
As a result of the widespread use of antibiotics, the appearance of infections caused by resistant organisms is on the rise
After synthesis and purification steps of SPPS the peptides were obtained as trifluoroacetate salts. trifluoroacetic acid (TFA)− can be found in peptides lyophilizates in two forms: as counterions to a positively charged side groups of peptides and as a free trifluoroacete
We determined the content of TFA− in peptides and their retro analogs by ion chromatography using the validated procedure
Summary
As a result of the widespread use of antibiotics, the appearance of infections caused by resistant organisms is on the rise. Acquisition of the non-susceptibility to antibiotics is related to the circulation of genes in the environment and resistance determinants can be transferred to pathogenic microorganisms. The spread of these pathogens has been related to various epidemiological factors such as the lack of appropriate procedures in the healthcare facilities and the international transfer of patients coming from endemic areas (e.g., spread of carbapenem-resistant Klebsiella pneumoniae in Europe) (Girmenia et al 2016). Increasing rate of multi-resistant bacteria forces the need of development of new antimicrobial substances that could be applicable in therapy
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