Paclitaxel （PTX） is one of the most efficient anticancer drugs for the treatment of cancers through β-tubulin-binding. Our previous work indicated that a PTX-derivative hydrogelator Fmoc-Phe-Phe-Lys（paclitaxel）-Tyr（H2PO3）-OH （1）could promote neuron branching but the underlying mechanism remains unclear. Using tubulin assembly-disassembly assay, in this work, we found that compound 1 obviously delayed more microtubule aggregation than PTX did. Under the catalysis of alkaline phosphatase, Fmoc-Phe-Phe-Lys（paclitaxel）- Tyr（H2PO3）-OH could self-assemble into nanofiber Fmoc-Phe-Phe-Lys（paclitaxel）-Tyr-OH with width comparable to the size of αβ-tubulin dimer. Therefore, we proposed in this work that nanofiber Fmoc-Phe-Phe-Lys（paclitaxel）-Tyr-OH not only inhibits the αβ-tubulin dimer binding to each other but also interferes with the plus end aggregation of microtubule. This work provides a new mechanism of the inhibition of microtubule formation by a PTX- derivative hydrogelator.
