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

• Published in: Amino acids 2017-10, Vol.49 (10), p.1755-1771
• Main Authors: Neubauer, Damian, Jaśkiewicz, Maciej, Migoń, Dorian, Bauer, Marta, Sikora, Karol, Sikorska, Emilia, Kamysz, Elżbieta, Kamysz, Wojciech
• Format: Article
• Language: English
• Subjects: Amphibian Proteins - chemistry; Amphibian Proteins - pharmacology; Analogs; Analytical Chemistry; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial peptides; Bacteria; Biochemical Engineering; Biochemistry; Biological properties; Biomedical and Life Sciences; Circular dichroism; Dichroism; Drug resistance; Erythrocytes; Fungi; Gram-negative bacteria; Helicity; Hemolysis; High performance liquid chromatography; Hydrophobicity; Klebsiella; Klebsiella pneumoniae - growth & development; Life Sciences; Microorganisms; Neurobiology; Original; Original Article; Peptides; Proteomics; Reversion; Self-assembly; Self-association; Temperature profiles
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-017-2473-7

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.