Paclitaxel Hydrogelator Delays Microtubule Aggregation

摘要

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.