Cytotoxic activity of recombinant bFGF-rViscumin fusion proteins.

Abstract:

:A fusion protein (bFGF-rMLA), containing the mitogen basic fibroblast growth factor (bFGF) and the cytotoxic component of rViscumin (recombinant mistletoe lectin), the enzymatic A-chain (rMLA), was expressed in Escherichia coli, purified, and functionally characterized. bFGF-rMLA is cytotoxic for mouse B16 melanoma cells expressing the FGF receptor with an IC(50) value of approximately 1 nM. rMLA shows no significant effect on the viability of the B16 cells up to a concentration of 141 nM. Additionally, bFGF-rMLA was associated with the rViscumin B-chain (rMLB) in an in vitro folding procedure. The IC(50) value of bFGF-rMLA/rMLB to B16 cells in the presence of lactose-to block rMLB lectin activity-was 134 pM. Thus, it was possible to enhance the efficacy of a rViscumin A-chain mitotoxin through addition of rMLB. We conclude that rViscumin fusion proteins may be generally applicable for the receptor-specific inactivation of target cells and point out their potential in drug development.

authors

Schmidt A,Möckel B,Eck J,Langer M,Gauert M,Zinke H

doi

10.1006/bbrc.2000.3697

subject

Has Abstract

pub_date

2000-10-22 00:00:00

pages

499-506

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(00)93697-0

journal_volume

277

pub_type

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