Issue 41, 2022, Issue in Progress

Reactions of proteins with a few organopalladium compounds of medicinal interest

Abstract

Pd compounds form a promising class of experimental anticancer drug candidates whose mechanism of action is still largely unknown; in particular, a few organopalladium compounds seem very attractive. To gain mechanistic insight into medicinal palladium compounds, we have explored here – through ESI MS analysis – the interactions of four organopalladium agents (1–4) – showing remarkable in vitro antiproliferative properties – with a few representative model proteins, i.e., lysozyme (HEWL), ribonuclease A (RNase), and carbonic anhydrase (hCAI). The tested panel included three Pd allyl compounds with one or two carbene ligands and a palladacyclopentadienyl complex. Notably, the Pd allyl compounds turned out to manifest, on the whole, a modest tendency to react with the above proteins. Only complex 3 produced small amounts of characteristic adducts with hCAI bearing either one or two Pd allyl groups. In contrast, the palladacyclopentadienyl complex 4 manifested a greater and peculiar reactivity with all the above proteins generating invariably protein adducts with a mass increase of +256 Da where a butadienyl group – with no associated Pd – is attached to the proteins. Afterwards, we extended our investigations to the C-terminal dodecapeptide of thioredoxin reductase bearing the –Cys–Sec– reactive motif. In this latter case adducts were formed with all tested Pd compounds; however, complex 4 manifested towards this dodecapeptide a type of reactivity deeply different from that observed with HEWL, RNase A and hCAI. The mechanistic implications of these findings are discussed.

Graphical abstract: Reactions of proteins with a few organopalladium compounds of medicinal interest

Supplementary files

Article information

Article type
Paper
Submitted
25 Aug 2022
Accepted
30 Aug 2022
First published
21 Sep 2022
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2022,12, 26680-26685

Reactions of proteins with a few organopalladium compounds of medicinal interest

L. Massai, T. Scattolin, M. Tarchi, F. Visentin and L. Messori, RSC Adv., 2022, 12, 26680 DOI: 10.1039/D2RA05332B

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