REDUCING THE HETEROGENEITY OF CHEMICALLY CONJUGATED TARGETED TOXINS - HOMOGENEOUS BASIC FGF-SAPORIN

被引:18
作者
LAPPI, DA
MATSUNAMI, R
MARTINEAU, D
BAIRD, A
机构
[1] The Whittier Institute for Diabetes and Endocrinology, Department of Molecular and Cellular Growth Biology, La Jolla, CA 92037
关键词
D O I
10.1006/abio.1993.1353
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Basic fibroblast growth factor-saporin (FGF-SAP) is an extremely potent cytotoxic agent for cells bearing the FGF receptor. For its synthesis, the two free cysteines on the surface of basic FGF are available for linking by disulfide bridge to SAP which has been derivatized with a reactive sulfhydryl. Because of the heterogeneous nature of the synthesis, the resulting conjugate is heterogeneous as judged by gel electrophoresis. We have removed by site-directed mutagenesis one of the reactive cysteines of basic FGF and have purified monoderivatized SAP to use as the reactants. The resulting chemical conjugate shows a single band containing only 1 mol of basic FGF and 1 mol of SAP per molecule. This homogeneous conjugate is a potent cytocidal agent to cells bearing the FGF receptor. © 1994 Academic Press, Inc. All rights reserved.
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页码:446 / 451
页数:6
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