Polyvalent Presentation of Membrane-Lytic Peptides Enhances Antitumor Potency

A membrane-lytic peptide-polymer conjugate was constructed and the relation between peptide loading and activity was investigated by systematically varying the peptide density. A short membrane-lytic sequence was conjugated to dextran at different densities. The resulting conjugates were then applied to tumor cells for cytotoxicity test. Compared to free peptides, the potency of templated peptides was significantly enhanced by three orders of magnitude. And the lysing activity was found to be positively correlated to loading. We hypothesize that the pre-assembly enables polyvalent presentation of lytic peptides, thus facilitate the cooperative membrane-lysing process.