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Acyloxymethyl esterification of nodularin-R and microcystin-LA produces inactive protoxins that become reactivated and produce apoptosis inside intact cells.

Abstract：

:We report the esterification of the carboxyl groups of the cyclic peptide toxins nodularin-R and microcystin-LA to produce stable diacetoxymethyl and dipropionyloxymethyl ester derivatives. The derivatives had no activity but were reactivated upon esterase treatment. When injected into cells, the acyloxymethyl moieties were cleaved off and apoptosis induced. Linking the acyloxymethyl-ester moiety of these potent toxins to carriers destined for endocytosis paves the way for selective apoptosis induction in target (e.g., cancer) cells.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Herfindal L,Kasprzykowski F,Schwede F,Łankiewicz L,Fladmark KE,Łukomska J,Wahlsten M,Sivonen K,Grzonka Z,Jastorff B,Døskeland SO

doi

10.1021/jm900502e

subject

Has Abstract

pub_date

2009-09-24 00:00:00

pages

5758-62

issue

18

eissn

0022-2623

issn

1520-4804

journal_volume

52

pub_type

杂志文章

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