MAF-10L

MAF-10L is a membrane-disrupting agent and a cationic amphiphilic honeybee venom peptide AF derivative that features an enhanced α-helical structure. MAF-10L preferentially interacts with DOPS lipids in cancer cell membranes, leading to membrane disruption and subsequent leakage. MAF-10L is applicable in cancer research.

MAF-10L (50 µM) exhibits the highest α-helix content among the tested derivatives, with a helicity of 48.7% in PBS and 99.7% in 10% SDS. It shows the strongest self-association tendency within the MAF series. MAF-10L (0.39-200 µM; 6 hours) demonstrates potent anticancer activity against **4T1**, **B16F10**, **CT26**, **A549**, and **Hep3b** cells, with IC50 values ranging from 2.4 to 9.2 µM. At concentrations between 4-128 µM, MAF-10L (20 minutes) exhibits enhanced hemolytic activity on red blood cells (RBCs), with increasing concentration leading to a higher percentage of hemolysis. MAF-10L (5-10 μM; 1 hour) damages the plasma membrane of A549 cells, resulting in increased PI uptake. During a 50 ns MD simulation in aqueous solution, MAF-10L (50 ns) maintains a complete α-helix structure. It can translocate across a cancer cell membrane model, achieving this with low energy barriers and minimal lipid interference, a process supported by its α-helix structure. MAF-10L (2 µM; 6 h) can trigger features of immunogenic cell death in cancer cells, including the upregulation of calreticulin and the release of ATP.