Synthesis of Cell Growth Inhibitor Dolastatin 15 Analogues and Their Activities

Chem. J. Chinese Universities

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Synthesis of Cell Growth Inhibitor Dolastatin 15 Analogues and Their Activities

QIE Jian-Kun, LIANG Yuan-Jun, WU Ping, HE Jun-Lin, ZHAO Xiu-Nan, ZHOU Wen-Xia, ZHANG Yong-Xiang, LIU Ke-Liang^*

Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China

Received:2008-07-07 Revised:1900-01-01 Online:2009-02-10 Published:2009-02-10
Contact: LIU Ke-Liang

Abstract

Abstract: Dolastatin 15(D15)was a linear depsipeptide with two N-methylated valines and a complex C-terminal, showing potent cell growth inhibitory activity. D15 was highly alkylation and with spacial constraints. Modifications at D15’s N-terminal were performed by introducing three unnatural amino acid analogs 1—3 with more conformation-restriction and hydrophobicity. Twenty-one compounds were synthesized, and their activities were evaluated in vitro on human tumor cell lines K562, OVCA2780 and Kato-Ⅲ. Some compounds exhibited modest potency compared to compound LU103793, an analog of D15, evaluated in clinical phase Ⅱ now. A primary structure-activity relationship was summarized about the N-terminal.

Key words: Cell growth inhibitor, Dolastatin 15 analogs, Linear peptide, Marine bioactive peptide

CLC Number:

O629

TrendMD:

QIE Jian-Kun, LIANG Yuan-Jun, WU Ping, HE Jun-Lin, ZHAO Xiu-Nan, ZHOU Wen-Xia, ZHANG Yong-Xiang, LIU Ke-Liang^*. Synthesis of Cell Growth Inhibitor Dolastatin 15 Analogues and Their Activities[J]. Chem. J. Chinese Universities, doi: .

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Synthesis of Cell Growth Inhibitor Dolastatin 15 Analogues and Their Activities

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