Developing Potent and Selective Anticancer Therapy through Chemical Approaches and the Combination of Cationic Amphipathic Oncolytic Peptides

This study explores the structure–activity
relationships
of cationic amphipathic Mastoparan AF derivatives and their combination
with the oncolytic peptide LTX315 to enhance the anticancer
efficacy. The original peptide was modified to improve its selective
interaction with cancer cell membranes, thereby increasing anticancer
potency while minimizing hemolytic activity. Circular dichroism spectroscopy
and molecular dynamics simulations were employed to evaluate structural
changes and self-association tendencies. Among the derivatives, MAF-10L exhibited superior anticancer activity but elevated
hemolysis, which was mitigated through combination therapy with LTX315. These findings underscore the potential of cationic
amphipathic peptides as a basis for selective anticancer treatments
and highlight the benefits of peptide combinations in reducing adverse
effects while enhancing the therapeutic efficacy.