Pep5-Cpp, a Cyclin D2-Derived Antimicrobial

Peptidomic studies in <i>HeLa</i> 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 <i>Staphylococcus aureus</i>, MIC values were 6.25 µM for Pep5-Cpp and ΔC3-Pep5-Cpp and 12.5 µM for ΔN-Pep5-Cpp. Against <i>Candida albicans</i>, Pep5-Cpp showed a MIC of 3.125 µM, while both derivatives presented 6.25 µM. For <i>Aspergillus niger</i>, MIC values were 1.56 µM for Pep5-Cpp and ΔN-Pep5-Cpp, and 25 µM for ΔC3-Pep5-Cpp. Pep5-Cpp interacted with <i>S. aureus</i> DNA, increased fluorescence in <i>S. aureus</i>, and showed no change in <i>C. albicans</i>. Only ΔC3-Pep5-Cpp inhibited biofilm (>50%). Microbicidal assays showed that high concentrations were needed to kill <i>S. aureus</i> (>100 µM), while lower concentrations completely inhibited <i>C. albicans</i> (<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.