JOURNAL OF SHANDONG UNIVERSITY(NATURAL SCIENCE) ›› 2019, Vol. 54 ›› Issue (7): 35-41.doi: 10.6040/j.issn.1671-9352.0.2018.264

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Synthesis of novel taxoid-biotin conjugate

Yun-rong JING1(),Chang-wei WANG2   

  1. 1. Mudanjiang Normal University, Department of Pharmaceutical Engineering, Mudanjiang 157011, Heilongjiang, China
    2. Guangzhou Institute of Biomedicine and Health, Chinese Academy of Science, Guangzhou 510530, Guangdong, China
  • Received:2018-05-15 Online:2019-07-20 Published:2019-06-27
  • Supported by:
    黑龙江省教育厅资助项目(1353MSYQN011);黑龙江省自然科学基金资助项目(QC2015014);牡丹江市科学技术计划研究项目(Z2016s0026);牡丹江师范学院博士科研启动基金(MNUB201405)

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Abstract:

The conjugate is designed to be specific to the biotin receptors overexpressed on tumor cell surface and internalized efficiently through receptor-mediated endocytosis, followed by smooth drug release via glutathione-triggered self-immolation of the linker. An efficient mechanism-based tumor-targeting drug delivery system, based on tumor-specific biotin-receptor mediated endocytosis, has reduced the undesirable side effects associated with the traditional cytotoxic chemotherapeutic agents which lack of selectivity to tumor cells and normal cells. The disulfide linker is prepared by subsititution of sulfhydryl group. The tumor-targeting molecule biotin moiety is prepared by conversion of carboxylic acid group to acyl hydrazide group. Fluorotaxane SB-T-12854 with anti multidrug resistance is choosed as th cytotoxic agent. The tumor-targeting drug delivery system is a novel conjugate of a cytotoxic agent (SB-T-12854), a disulfide linker and a tumor-targeting molecule (biotin).

Key words: tumor-specific drug delivery system, taxoid, biotin, conjugate

CLC Number: 

  • R965.1

Fig.1

Mechanism of the self-immolative disulfide linker"

Fig.2

SB-T-12854 and biotin-linker-SB-T-12854 conjugate"

Fig.3

Synthesis of biotin-linker-SB-T-12854 conjugate"

Fig.4

Fluorogenic probes"

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