To optimize Indolicidin's efficacy against Gram-negative bacteria, increasing the peptide's cationicity was necessary, leading to the development of CP-11 (PDB ID: 1qxq) . A macrocyclic variant, cyclo-CP-11 (PDB ID: 1qx9), was synthesized to improve the peptide's half-life by reducing susceptibility to proteolytic degradation by trypsin enzymes, which commonly cleave basic, Arg-rich peptides. Cyclo-CP-11 demonstrated prolonged stability in the presence of trypsin , illustrating how cyclization can enhance the pharmacokinetic properties of AMPs. Both CP-11 and cyclo-CP-11 retained low minimum inhibitory concentrations (MIC) against Gram-positive bacteria . CP-11 peptide has better hemolytic profile compared to Indolicidin , confirming the hypothesis that a reduction in hydrophobicity may reduce hemolytic activity . The researchers also observed that intracellular effects on the DNA biosynthesis pathway and downstream ones (RNA and protein synthesis) were still conserved in both .