186097-60-9Relevant academic research and scientific papers
Peptidomimetic Glutathione Analogues as Novel γGT Stable GST Inhibitors
Burg, Danny,Filippov, Dmitri V,Hermanns, Ralph,Van der Marel, Gijs A,Van Boom, Jacques H,Mulder, Gerard J
, p. 195 - 205 (2002)
Elevated levels of glutathione-S-transferase (GST) isoenzymes are found in many tumor cells and are thought to play a role in the onset of multidrug resistance (MDR). To evaluate the contribution of GST to this process, inhibitors are needed. Glutathione (GSH) conjugates, although good GST inhibitors, cannot be used in vivo, because they are eliminated rapidly. In this paper, we describe the synthesis of a series of novel peptidomimetic glutathione analogues that are stabilized against peptidase mediated breakdown. The peptide bonds in GSH were replaced by isosteres, such as the 'reduced' amide (which was prepared using a novel method), N-methylamide, urethane, and methylene linkages. The in vitro evaluation of the compounds focuses on GST inhibition and stability towards γ-glutamyl-transpeptidase (γGT), the main enzyme involved in GSH breakdown. The compounds were conjugated to the model electrophile ethacrynic acid (EA) to resemble GS-EA, an efficient GST inhibitor. All novel GSH-analogues were shown to inhibit rat liver cytosolic GSTs. Furthermore, peptidometric changes of the γ-glutamyl-cysteine amide bond greatly improved stability towards γGT. These compounds may be useful in the design of novel in vivo applicable GST inhibitors. Copyright
Synthesis and activity of the glutathione analogue γ-(L-γ-oxaglutamyl)-L-cysteinyl-glycine
Calcagni, Anna,Dupre, Silvestro,Lucente, Gino,Luisi, Grazia,Pinnen, Francesco,Rossi, Domenico,Spirito, Alessandra
, p. 498 - 502 (1996)
An efficient synthesis of the backbone modified glutathione analogue γ-(L-γ-oxaglutamyl)-L-cysteinyl-glycine (7), characterized by the presence of an urethane O-CO-NH linkage replacing the γ-glutamylic CH2CO-NH fragment is described. The new an
Peptide-bond modified glutathione conjugate analogs modulate GSTπ function in GSH-conjugation, drug sensitivity and JNK signaling
Burg, Danny,Riepsaame, Joey,Pont, Chantal,Mulder, Gerard,Van De Water, Bob
, p. 268 - 277 (2007/10/03)
Glutathione S-transferase π (GST, E.C.2.5.1.18) overexpression contributes to resistance of cancer cells towards cytostatic drugs. Furthermore, GSTπ is involved in the cellular stress response through inhibition of Jun N-terminal-kinase (JNK), a process t
