How to Improve the RRWQWR Anticancer Activity? Strategy I: Chimera Building

Abstract Cervical cancer currently affects thousands of women worldwide. Consequently, the search for new peptide molecules, particularly chimeric peptides, has been proposed to treat this disease. In the present study, a library of chimeric peptides containing the RRWQWR sequence conjugated to functional peptides (such as anticancer peptides, cervical cancer cell‐targeting peptides, and cell‐penetrating peptides) was designed and synthesized. The most active chimera was optimized through chemical modifications, including the replacement of Arg with Lys, formation of dimers, changes in the linker, and deletion of amino acids at the N‐ and/or C‐terminus. All chimeric peptides were obtained via solid‐phase peptide synthesis and characterized by means of RP‐HPLC and mass spectrometry. The cytotoxicity of the chimeras against human cervical cancer cell lines HeLa and Ca Ski was evaluated in vitro. The results demonstrated that it is possible to obtain chimeric peptides from the RRWQWR core conjugated with functional peptides. Some peptides exhibited significant cytotoxic activity against the evaluated cell lines, demonstrating selectivity, rapid action, and concentration dependence. The chimeric peptide library allowed the identification of promising chimeric peptides such as KKWQWK‐Ahx‐RLLRRLLR. The identification of molecules with anticancer activity from sequences with lower activity represents a rapid, cost‐effective, and highly accurate strategy.