Significantly enhanced proteolytic activity of cyclen complexes by monoalkylation

Abstract

A simple approach towards efficient artificial proteases based on the cyclen ligand is presented. We thus achieved an increase of the proteolytic activity of two orders of magnitude when compared to the unsubstituted cyclen complex. Amphiphilic Cu(ii) and Co(iii) complexes cut BSA and myoglobin as model substrates at μM concentrations. MALDI-ToF MS is used to identify the cleavage fragments.

Monoalkylated Cyclen Complexes for Efficient Proteolysis: Influence of Donor Atom Exchange

“…Similar energy barriers were calculated for the cleavage reaction catalyzed by Co(III) cyclen and Co(III) oxacyclen, which the authors saw in accordance with experimental results – despite of the oxygen analog being four‐ to fourteen‐fold more efficient as derived from the experiments . Indeed, the cleavage activities of Cu(II) and Co(III) complexes are comparable, for which DFT calculations gave similar energy barriers.…”

“…In previous studies we reported the cleavage of BSA by alkylated derivatives of Cu(II) cyclen perchlorato complexes (Figure ) . A correlation between the cleavage efficiency and the length of the attached alkyl chain was observed for that system.…”

“…In contrast, a remarkable drop in activity occurs for 9 , the complex with a C 10 chain. In this case, a full cleavage of BSA takes place only at considerably higher concentration of 500 μM . Taking into account the aforementioned results the cleavage of BSA was investigated within this study at near‐physiological conditions (pH 7.4 MOPS‐NaOH, 37 °C, 1.05 μM BSA concentration, 24 h).…”

“…This has also been shown for the hydrolytic cleavage of the phosphate backbone in RNA and DNA ,. For protein cleavage, cyclen and oxacyclen complexes, however, require non‐physiological conditions (50 °C, pH ≥ 9), concentrations in the mM range and long incubation times ,. An important prerequisite for controlled cleavage reactions is the stability of the applied metal complexes.…”

“…An enhancement of cleavage activity was observed with increasing chain length. As for most of the above mentioned examples, however, elevated temperatures, increased pH values and long incubation times were necessary …”