Antibody Conjugates with Morpholinodoxorubicin and Acid-Cleavable Linkers

被引：60

作者：

Mueller, Barbara M. ^{[1
]}

Wrasidlo, Wolf A. ^{[2
]}

Reisfeld, Ralph A. ^{[1
]}

机构：

[1] Scripps Clin & Res Fdn, La Jolla, CA 92037 USA

[2] Biotechnetics, San Diego, CA 92121 USA

来源：

BIOCONJUGATE CHEMISTRY | 1990年 / 1卷 / 05期

关键词：

D O I：

10.1021/bc00005a005

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Antibody-morpholinodoxorubicin conjugates were prepared for targeted immunotherapy of human melanoma. Spacer molecules that differ in hydrolytic stability were employed between the C-13 of the drug and amino residue of lysine on the monoclonal antibody. Antibody-drug conjugates were made with five structurally different morpholinodoxorubicin derivatives including oxime, phenylhydrazone, (sulfonylphenyl)hydrazone, and acylhydrazone moieties. Hydrolytic stability of the antibody conjugates directly correlated with their in vitro cytotoxicity against melanoma cells. Derivatives or conjugates with the greatest hydrolytic stability showed the least cytotoxicity.

引用

页码：325 / 330

页数：6

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