pH-tuned metal coordination and peroxidase activity of a peptide dendrimer enzyme model with a Fe(<scp>ii</scp>)bipyridine at its core
作者:Piero Geotti-Bianchini、Tamis Darbre、Jean-Louis Reymond
DOI:10.1039/c2ob26551f
日期:——
Peptide dendrimer BP1 was obtained by double thioether bond formation between 5,5′-bis(bromomethyl)-2,2′-bipyridine and two equivalents of peptide dendrimer N1 (Ac-Glu-Ser)8(Dap-Glu-Ala)4(Dap-Amb-Tyr)2Dap-Cys-Asp-NH2 (Dap = branching 2,3-diaminopropanoic acid, Amb = 4-aminomethyl-benzoic acid). At pH 4.0 BP1 bound Fe(II) to form the expected tris-coordinated complex [FeII(BP1)3] (Kf = 2.1 × 1015 M−3). At pH 6.5 a monocoordinated complex [FeII(BP1)] was formed instead (Kf = 2.1 × 105 M−1) due to electrostatic repulsion between the polyanionic dendrimer branches, as confirmed by the behavior of three analogues where glutamates were partially or completely replaced by neutral glutamines or positive lysines. [FeII(BP1)] catalyzed the oxidation of o-phenylenediamine with H2O2 with enzyme-like kinetics (kcat = 1.0 min−1, KM = 1.5 mM, kcat/kuncat = 90 000) and multiple turnover, while Fe2+ or [Fe(bipy)3]2+ were inactive. The labile coordination positions allowing coordination to H2O2 and to the substrate are likely responsible for the enhanced peroxidase activity of the metallopeptide dendrimer.
肽树枝状聚合物 BP1 是由 5,5′-双(溴甲基)-2,2′-联吡啶和两个等量的肽树枝状聚合物 N1 (Ac-Glu-Ser)8(Dap-Glu-Ala)4(Dap-Amb-Tyr)2Dap-Cys-Asp-NH2 (Dap = 支链 2,3-二氨基丙酸,Amb = 4-氨基甲基苯甲酸)之间形成双硫醚键而得到的。在 pH 值为 4.0 时,BP1 与铁(II)结合,形成预期的三配位复合物 [FeII(BP1)3](Kf = 2.1 × 1015 M-3)。在 pH 值为 6.5 时,由于多阴离子树枝状聚合物分支之间的静电排斥作用,反而形成了单配位复合物 [FeII(BP1)](Kf = 2.1 × 105 M-1),这一点在谷氨酸部分或全部被中性谷氨酸或正赖氨酸取代的三种类似物的行为中得到了证实。[FeII(BP1)] 催化邻苯二胺与 H2O2 的氧化,具有类似酶的动力学(kcat = 1.0 min-1,KM = 1.5 mM,kcat/kuncat = 90 000)和多次周转,而 Fe2+ 或 [Fe(bipy)3]2+ 则没有活性。金属肽树枝状聚合物之所以能增强过氧化物酶的活性,很可能是因为它的易配位位置允许与 H2O2 和底物配位。