title: Development of a functional cis-prolyl bond biomimetic and mechanistic implications for nickel superoxide dismutase.
abstract: 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.
authors.affiliation: Technische Universität Darmstadt, Eduard-Zintl-Institut für Anorganische und Physikalische Chemie, Petersenstr. 22, 64287 Darmstadt, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tietze
authors.forename: Marco
authors.initials: M
authors.lastname: Tischler
authors.forename: Stephan
authors.initials: S
authors.lastname: Voigt
authors.forename: Diana
authors.initials: D
authors.lastname: Imhof
authors.forename: Oliver
authors.initials: O
authors.lastname: Ohlenschläger
authors.forename: Matthias
authors.initials: M
authors.lastname: Görlach
authors.forename: Gerd
authors.initials: G
authors.lastname: Buntkowsky
mesh_terms: D032701:Biomimetics; D002384:Catalysis; D018360:Crystallography, X-Ray; D003500:Cyclization; D008968:Molecular Conformation; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D011407:Propane / Q000737:chemistry*; D011487:Protein Conformation; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010455:Peptides; D009532:Nickel; D013482:Superoxide Dismutase; D011407:Propane