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Paclitaxel Hydrogelator Delays Microtubule Aggregation
Bin Mei,Gao-lin Liang*
Author NameAffiliationE-mail
Bin Mei CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei 230026, China;Department of Biology, College of Life Science, Anhui Medical University, Hefei 230032, China  
Gao-lin Liang* CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei 230026, China gliang@ustc.edu.cn 
Abstract:
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 hydroge-lator 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.
Key words:  Paclitaxel  Hydrogelator  Microtubule  Aggregation
FundProject:This work was supported by the Ministry of Sci-ence and Technology of China (No.2016YFA0400904) and the National Natural Science Foundation of China (No.U1532144 and No.21675145)
紫杉醇水凝胶成胶因子延缓微管蛋白聚集
梅斌,梁高林*
摘要:
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DOI:10.1063/1674-0068/30/cjcp1609179
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