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The Hybrid Pyrroloisoindolone–Dehydropyrrolizine Alkaloid (−)‐Chlorizidine A Targets Proteins within the Glycolytic Pathway
Author(s) -
ÁlvarezMicó Xavier,
Rocha Danilo D.,
Guimarães Larissa A.,
Ambrose Andrew,
Chapman Eli,
CostaLotufo Leticia V.,
La Clair James J.,
Fenical William
Publication year - 2015
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500229
Subject(s) - alkaloid , biochemistry , cytosol , chemistry , fusion protein , glyceraldehyde 3 phosphate dehydrogenase , glycolysis , computational biology , biology , enzyme , stereochemistry , recombinant dna , gene , dehydrogenase
The cytotoxic activity of (−)‐chlorizidine A, a marine alkaloid containing a unique fusion between a pyrroloisoindolone and dehydropyrrolizine, was explored by using a combination of cellular and molecular methods. Our studies began by applying preliminary SAR evidence gathered from semisynthetic bioactivity evaluations to prepare an active immunoaffinity fluorescent (IAF) probe. This probe was then used to identify two cytosolic proteins, GAPDH and hENO1, as the targets of (−)‐chlorizidine A.