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）-...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.展开更多
基金This work was supported by the Ministry of Science and Technology of China （No.2016YFA0400904） and the National Natural Science Foundation of China （No.U1532144 and No.21675145）.
文摘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.
