The cytotoxicity of Pseudomonas exotoxin A, inactivated by modification of the cell-binding domain I, is restored when conjugated to an erythroid cell-specific targeting agent.

Abstract:

:To be capable of selective killing of tumor cells, the non-selective Pseudomonas aeruginosa exotoxin A must have its cell-binding domain inactivated or removed and then be chemically linked to, or genetically fused with, a specific targeting agent. In the present study, epsilon-NH2 groups of lysine residues of the cell-binding domain of exotoxin A were extensively propionylated with N-succinimidyl-3-propionate (NSP). The NSP-treated exotoxin retained its cytocidal ADP-ribosyltransferase activity, but it could no longer bind to, and inhibit the proliferation of, Friend murine erythroleukemia cells. Cytotoxicity (i.e., the ability to inhibit proliferation) for the Friend erythroid cells was restored completely to the NSP-inactivated exotoxin by conjugating it to ADIF, an autocrine factor secreted by chicken erythroleukemia cells which selectively inhibits the differentiation of erythroid cells such as Friend erythroleukemia cells without inhibiting their proliferation.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Bourdenet S,Doyonnas R,Vacheron MJ,Guinand M,Fasciotto B,Ristic A,Michel G,Cozzone AJ,Durkin JP,Whitfield JF

doi

10.1016/0304-3835(90)90241-o

subject

Has Abstract,Author List Incomplete

pub_date

1990-04-20 00:00:00

pages

121-7

issue

2

eissn

0304-3835

issn

1872-7980

pii

0304-3835(90)90241-O

journal_volume

50

pub_type

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