Glycosidase- and β-lactamase-like activity of dinuclear copper(II) patellamide complexes

Is CuII Coordinated to Patellamides inside Prochloron Cells?

“…Imaging by flow cytometry and confocal microscopy has implied that a Cu II –patellamide complex forms in the Prochloron cells, as observed in vitro. The formation of Cu II complexes inside Prochloron cells indicates that the catalysis of various hydrolysis reactions observed in vitro, such as those of carbonic anhydrase, phosphatase, lactamase, and glycosidase, and possibly others not yet explored, might be the metabolic purpose of patellamides. The corresponding Zn II complexes, which have also been shown to form and to be catalytically active, are less likely to be of biological relevance, and the Cu II complexes might therefore be a rare case of Cu II hydrolase enzymes.…”

“…Small cyclic octapeptides extracted from the blue‐green algae Prochloron have been the subject of extensive investigations regarding their putative biological role . They are commonly referred to as “patellamides”, as they were initially isolated from the sea squirt Lissoclinum patella , the host of Prochloron .…”

“…To shed light on the biological role of the patellamides, hydrolase studies were conducted, which showed that dinuclear Cu II complexes of the synthetic peptides served as potent phosphatase and carbonic anhydrase mimics at pH 7–8 . At pH 10–11, α‐ and β‐glycosidase as well as β‐lactamase activity was observed, giving rise to the idea that metal complexes of the cyclic peptides might act as pH‐dependent catalysts. This is underpinned by a study that showed the pH in L. patella to vary greatly, from 7.5 in darkness to almost 11 in light .…”

Metal‐coordinated Hydroxide as a Nucleophile: a Brief History

“…Indeed they do. In an extensive series of papers Comba and his group have studied the Cu II and Zn II complexes of analogues of the patellamides . What is most significant in the sense of this present article is that the Cu II and Zn II complexes of these patellamide analogues exhibit hydrolytic activity towards a number of substrates through a nucleophilic M –OH moiety (Scheme ).…”

“…We end by highlighting some work involving metal‐coordinated hydroxide carried out by the dedicatee of this review, Professor Peter Comba. Comba and his associates have studied the chemistry of cyclic octapeptides, synthetic analogues of marine metabolites found in ascidians of the Pacific and Indian Oceans and originally isolated from genus Lissoclinum bistratum and Lissoclinum patella , . The ascidians (or tunicates) are filter‐feeding animals, found as individuals or in colonies on the ocean floor and importantly metabolites isolated from these animals exhibit antiviral, antitumor and cytotoxic properties.…”