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Australian Journal of Chemistry
Volume 64
Number 12 2011
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Antitumor Activities and Structure–Activity Relationship of Phosphotriester Derivatives of Homocamptothecin Based on a Semisynthetic Route

Yong-Qiang Zhang, Huo-Jun Zhang, Jing Zhang, Juan Wang, Jian-Zhong Yao, Lin-Jian Zhu, Chun-Lin Zhuang, Sheng-Zheng Wang, Guo-Qiang Dong, Chun-Quan Sheng, Zhen-Yuan Miao and Wan-Nian Zhang

pp. 1547-1553

Based on a new semisynthetic route, a series of phosphotriester 7-alkylhomocamptothecin derivatives are designed and synthesized. Cytotoxic activity assays show that compounds 12a and 14c have more potent activities than irinotecan, and compound 14c shows potent tumour inhibitory activity in a Colo205 xenograft model.
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PolyPEGylation of Protein using Semitelechelic and Mid-functional Poly(PEGMA)s synthesized by RAFT polymerization

Yingkai Liu, Mei Li, Dengxu Wang, Jinshui Yao, Jianxing Shen, Weiliang Liu, Shengyu Feng, Lei Tao and Thomas P. Davis

pp. 1602-1610

A series of well-defined semitelechelic and mid-functionalized poly(poly(ethylene glycol) methyl ether methacrylate)s (poly(PEGMA)s) were synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerization using thiazolidine-2-thione-functionalized chain transfer agents (CTAs). The thiazolidine-2-thione functionality located at the end of or at the middle of the polymer chains can react with amine residues on protein surfaces, forming protein-polymer conjugates via amide linkages. The protein conjugations from the mid-functionalized polymer remained much more protein bioactive compared to their semitelechelic counterpart with similar molecular weights, indicating that the steric hindrance of the mid-functionalized poly(PEGMA)s leads to the better selective conjugation to the protein. This synthetic methodology is suitable for universal proteins, seeking a balance between the protein bioactivity and the protein protection by the covalent linkage with polymers, and exhibits promising potential for pharmaceutical protein conjugation.
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