During recent years several peptide-based Ni superoxide dismutase (NiSOD) models have been developed. These NiSOD models show an important structural difference compared to the native NiSOD enzyme, which could cause a completely different mechanism of superoxide dismutation. In the native enzyme the peptide bond between Leu4 and Pro5 is cis-configured, while the NiSOD models exhibit a trans-configured peptide bond between these two residues. To shed light on how the configuration of this single peptide bond influences the activity of the NiSOD model peptides, a new cis-prolyl bond surrogate was developed. As surrogate we chose a leucine/alanine-based disubstituted 1,2,3-triazole, which was incorporated into the NiSOD model peptide replacing residues Leu4 and Pro5. The yielded 1,5-disubstituted triazole nickel peptide exhibited high SOD activity, which was approximately the same activity as its parent trans-configured analogue. Hence, the conformation of the prolyl peptide bond apparently has of minor importance for the catalytic activity of the metallopeptides as postulated in literature. Furthermore, it is shown that the triazole metallopeptide is forming a stable cyanide adduct as a substrate analogue model complex.
Water in site: The structure of a stable adduct of a peptide‐based nickel superoxide dismutase model (NiSOD) with cyanide as substrate analogue is determined by NMR spectroscopy and optimized by DFT methods. A functional water molecule is found in the active site (see picture; Ni brown, O red/pink, C green, N blue). The role of this water molecule in the catalytic degradation of O2.− is discussed.
Für ein stabiles Addukt aus einem peptidbasierten Modell der Nickel‐Superoxiddismutase (NiSOD) und Cyanid als Substratanalogon konnte die räumliche Struktur bestimmt und mit DFT‐Rechnungen optimiert werden. Nach den Rechnungen liegt im aktiven Zentrum ein funktionelles Wassermolekül vor (siehe Bild). Dessen Rolle für die katalytische Zersetzung von O2.− wird – auch im Zusammenhang mit anderen SODs – diskutiert.
Flower‐Power: Basierend auf der Struktur des Sunflower‐Trypsininhibitors 1 wurden Proteaseinhibitoren hergestellt, die Triazolylmimetika von cis‐ und trans‐Rückgrat‐Amiden enthalten. Das biologisch relevante cis‐Pro‐Motiv wurde durch eine nicht‐Prolyl‐Einheit ersetzt und röntgenstrukturanalytisch charakterisiert. Hochaufgelöste Kristallstrukturen von 1,4‐ und 1,5‐disubstituierten 1,2,3‐Triazolyl‐Peptidomimetika können als Strukturmotive für die Entwicklung maßgeschneiderter Bowman‐Birk‐Inhibitoren dienen.
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