Transition metal complexes of a cyclic pseudo hexapeptide: synthesis, complex formation and catalytic activities

Abstract

To contribute to a better understanding of metalloenzymes, we studied ion selectivity, complex formation tendencies and catalytic activities of linear and cyclic pseudopeptides. In this contribution, a linear and cyclic pseudo hexapeptide is described. The complex with transition metal ions and the sequence were designed using the programme COSMOS. Different routes of solid-phase synthesis were performed and compared using anchoring by C-terminus or a His side chain, using preformed pseudodipeptide building units or formation of N-functionalized peptide bond during stepwise assembly. The different strategies were compared regarding cyclization tendency, yield and purity. Side-chain anchoring to solid support favours the cyclization but leads to the formation of difficult to separate dioxopiperazine. Both routes require preformed building units. Complex-formation tendencies and selectivity for certain bivalent transition metal ions were experimentally estimated and compared to ones predicted theoretically. CD measurements indicate conformational changes by complex formation with different metal ions. Catalytic activities on oxidation of catechol and hydrolysis of bis-phosphate esters by some metal complexes of linear and cyclic peptide show only low catalytic activities compared to other model peptides and related metalloenzymes. The preference of the cyclic peptide for complexation of Ni(2+) corresponds well to the predictions of COSMOS-NMR force field calculations.