An increasing number of multidrug-resistant pathogens is a serious problem of modern medicine and new antibiotics are highly demanded. In this study, different n-alkyl acids (C₂-C₁₄) and aromatic acids (benzoic and trans-cinnamic) were conjugated to the N-terminus of KR12 amide. The effect of this modification on antimicrobial activity (ESKAPE bacteria and biofilm of Staphylococcus aureus) and cytotoxicity (human red blood cells and HaCaT cell line) was examined. The effect of lipophilic modifications on helicity was studied by CD spectroscopy, whereas peptide self-assembly was studied by surface tension measurements and NMR spectroscopy. As shown, conjugation of the KR12-NH₂ peptide with C₄-C₁₄ fatty acid chains enhanced the antimicrobial activity with an optimum demonstrated by C₈-KR12-NH₂ (MIC 1–4 μg/mL against ESKAPE strains; MBEC of S. aureus 4–16 μg/mL). Correlation between antimicrobial activity and self-assembly behavior of C₁₄-KR12-NH₂ and C₈-KR12-NH₂ has shown that the former self-assembled into larger aggregated structures, which reduced its antimicrobial activity. In conclusion, N-terminal modification can enhance antimicrobial activity of KR12-NH₂; however, at the same time, the cytotoxicity increases. It seems that the selectivity against pathogens over human cells can be achieved through conjugation of peptide N-terminus with appropriate n-alkyl fatty and aromatic acids.

The thermodynamic properties of micellization for dodecylphosphocholine (DPC), sodium dodecyl sulfate (SDS), and their mixtures were studied using isothermal titration calorimetry. NMR relaxation measurements were used to explore molecular mobility of the DPC-containing micelles, whereas the diffusion measurements were taken to determine the micelle size. The DPC/SDS mixed systems reveal a tendency to form two kinds of micelles in buffered solution at lower temperatures. An increase in temperature as well as the transfer of the DPC/SDS mixed micelles from buffered to unbuffered solution results in only a single-step micellization process. The average size of the DPC-containing micelles is only slightly dependent on the SDS fraction. Examination of the data of spin–spin relaxation (T ₂) shows that methylene protons on the polar headgroup of DPC and methylene protons (H1) on the hydrocarbon chain in the micellar systems studied reveal a heterogeneous dynamic behavior reflected in a two-component T ₂ relaxation in the whole temperature range. The latter is the main constituent of the rigid interfacial layer core protecting the penetration of water into the hydrophobic interior.

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.