Pep5-Cpp, a Cyclin D2-Derived Antimicrobial.

Peptidomic studies in HeLa cells identified the antitumoral activity of Pep5, and our group observed that coupling Pep5 to a carrier peptide (Cpp) provides antimicrobial potential. This study evaluated the antimicrobial activity of Pep5-Cpp and its derivatives (ΔC3-Pep5-Cpp and ΔN-Pep5-Cpp) and investigated their potential mechanisms of action. For Staphylococcus aureus, MIC values were 6.25 µM for Pep5-Cpp and ΔC3-Pep5-Cpp and 12.5 µM for ΔN-Pep5-Cpp. Against Candida albicans, Pep5-Cpp showed a MIC of 3.125 µM, while both derivatives presented 6.25 µM. For Aspergillus niger, MIC values were 1.56 µM for Pep5-Cpp and ΔN-Pep5-Cpp, and 25 µM for ΔC3-Pep5-Cpp. Pep5-Cpp interacted with S. aureus DNA, increased fluorescence in S. aureus, and showed no change in C. albicans. Only ΔC3-Pep5-Cpp inhibited biofilm (>50%). Microbicidal assays showed that high concentrations were needed to kill S. aureus (>100 µM), while lower concentrations completely inhibited C. albicans (<6.25 µM). In the hemolytic assay, the peptides at their MIC values did not induce measurable hemolysis. These findings indicate that Pep5-Cpp and its derivatives have antimicrobial potential and selectivity, supporting future pharmacological development.