Paclitaxel-Promoted Supramolecular Polymerization of Peptide Conjugates.

Spontaneous association above a threshold concentration is a hallmark of supramolecular polymerization, in which monomeric units self-assemble into polymeric aggregates through noncovalent interactions. This self-initiated supramolecular process differs from the conventional covalent chain-growth polymerization in that the latter often involves the use of a different chemical entity as an initiator to trigger/control the polymerization process. We report here the use of a small molecule hydrophobe, paclitaxel (PTX), as an effective promoter to induce the supramolecular polymerization of a peptide-paclitaxel conjugate, Spheropax (Spax). We found that Spax monomers alone in water self-assemble into spherical micelles of approximately 6.5 nm in diameter but, in the presence of free PTX, undergo a supramolecular polymerization process to form filamentous assemblies of several micrometers in length. Increasing the ratio of promoter to monomer (PTX/Spax) induces Spax's directional polymerization and expedites its kinetic process. We believe these findings provide important insight into the initiator-controlled supramolecular polymerization process.