Heme-peptide complexes as peroxidase models

Nicolis, Stefania; Casella, Luigi; Roncone, Raffaella; Dallacosta, Corrado; Monzani, Enrico

doi:10.1016/j.crci.2006.09.013

Cited by 20 publications

(14 citation statements)

References 55 publications

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“…Substantial research has gone into understanding the mechanistic details of peroxidases and making its functional mimics (Figure ). − Various metallo-porphyrin synthetic models of ferric peroxo, ferric hydroperoxide and, most importantly, compound I have been synthesized. The electronic structure of compound I could be tuned by modifying the porphyrin ring and as well as by varying axial ligands/counterions.…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, nanozymes face several critical issues primarily from biocompatibility, low binding affinity, and having an unknown mechanism which restricts their rational designing . Heme-peptide complexes can be employed to achieve peroxidase activity. Notable successes came through several approaches such as utilizing μ-peroxidase, mimochrome, re-engineered Mb, and, very recently, from de novo c-type cytochrome maquettes (CTMs) .…”

Section: Introductionmentioning

confidence: 99%

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Induction of Enzyme-like Peroxidase Activity in an Iron Porphyrin Complex Using Second Sphere Interactions

et al. 2019

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Emulating enzymatic reactivity using small molecules has been a long-time challenging pursuit of the scientific community. Peroxidases, ubiquitous heme enzymes that are involved in hormone synthesis and the immune system, have been a prime target of such efforts due to their tremendous potential in the chemical industry as well as in wastewater treatment. Here it is demonstrated that inclusion of a second sphere guanidine moiety in an iron porphyrin not only makes this small molecule a veritable peroxidase catalyst but also offers an auxiliary binding site for organic substrates, facilitating their rapid oxidation with a green oxidant like H2O2. This small molecule analogue exhibits a “ping–pong” mechanism and Michaelis–Menten type kinetics, which is generally typical of metallo-enzymes and follows a mechanism of the natural enzyme in its entirety, including the formation of compound I as the primary oxidant.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Induction of Enzyme-like Peroxidase Activity in an Iron Porphyrin Complex Using Second Sphere Interactions

et al. 2019

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“…indicates that this activity cannot be of any significance in vivo. In addition, it can be noted that the catalytic activity exhibited by heme model complexes which carry a positively charged distal residue mimicking the role of arginine in peroxidases, [19] as well as that of enzymes like horseradish peroxidase (HRP; Table 2) is larger by several orders of magnitude. This data implies that the proposed role exerted by Arg5 as an acid catalyst promoting cleavage of the peroxide O À O bond [16a] is negligible; no increase in peroxidase activity occurs upon adding free arginine to hemin-Ab16 (see the Supporting Information).…”

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confidence: 99%

Heme Binding Induces Dimerization and Nitration of Truncated β‐Amyloid Peptide Aβ16 Under Oxidative Stress

et al. 2013

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Several observations suggest a link between (ferric) heme and Alzheimers disease (AD), for example, an increase in heme oxygenase 1, [1,2] a loss of complex IV, [3][4][5][6] and abnormal iron metabolism. These observations suggest that heme metabolism is altered in age-related disorders. As a possible explanation, hemin has been proposed to interact with b-amyloid peptides (Ab), [7] and it is now well established that Ab peptides bind ferric heme. [8] The adducts of hemin-Ab peptides also exhibit increased peroxidase activity with respect to free hemin, [9] but these complexes have not been characterized. Herein we provide thermodynamic and spectroscopic data showing that hemin b can coordinate two Ab16 molecules to form the low-spin, six-coordinated complex [hemin(Ab16) 2 ], and this is in equilibrium with the high-spin [hemin(Ab16)] species, the relative amounts of which strongly depend on peptide concentration and temperature. In the presence of H 2 O 2 , hemin-Ab16 complexes produce dimerization of the peptide through dityrosine cross-linking, and in addition the peptide undergoes endogenous nitration at Tyr10 when nitrite is also present in solution. This result is important because both cross-linking and nitration at Tyr10 critically enhance Ab aggregation and plaque formation, [10] thus showing that the binding of heme to Ab can indeed be a factor contributing to neuroinflammation and Ab aggregation. The endogenous peroxidative (H 2 O 2 ) and nitrative (H 2 O 2 /NO 2 À ) activities exhibited by the hemin-Ab16 peptide add to, and are likely more deleterious than, the oxidation [9] and nitration [11] of external substrates which have been previously reported.Upon adding Ab16 to a 50 mm aqueous phosphate buffer solution of hemin b at pH 7.4 and 300 K, the broad Soret band of the complex near l = 385 nm progressively changes to give a sharp, red-shifted band at l = 414 nm, with additional visible bands at l = 535 and 566 nm (Figure 1 C, and see the Supporting Information). The conversion from the high-spin to the low-spin hemin species is complete after addition of 20 equivalents of Ab16, and spectrophotometric data analysis (see the Supporting Information) confirms a 2:1 Ab16/hemin stoichiometry, thus indicating the formation of the [hemin-(Ab16) 2 ] complex. The Mçssbauer and 1 H NMR spectra are consistent with a low-spin (S = 1/2) iron(III) center coordinated by two axial imidazole ligands. However, below saturating amounts of Ab16, the Mçssbauer spectrum clearly indicates the presence of a minor high-spin species (Figure 2). Figure 1. UV/vis spectra recorded in 50 mm phosphate buffer solution at pH 7.4. A) Hemin b (1.2 10 À5 m). B) Hemin b in the presence of an excess (20 equiv) of Ab16 peptide at 319 K. C) The same as (B) but at 300 K, the spectral changes are fully reversible. The D symbol indicates an increase in temperature.Figure 2. Mçssbauer spectrum of hemin b (2 mm), in the presence of 6 equivalents of the Ab16 peptide, recorded at 78 K. Quadrupole doublet simulation reveals the presence of a major...

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“…The sequence of Aβ(40/42) possesses several features similar to well-known heme peroxidases. For example, heme binding is mediated by a histidine, while an additional distal histidine and also a distal arginine are present. , To obtain more information on the possible impact of single residues within the 40mer Aβ-peptide, the catalytic activity of heme-incubated Aβ-derived peptides 1 – 6 was studied and compared to full-length Aβ(1–40). The aggregation state of Aβ(40) within the respective setups was tested using a thioflavin T fluorescence-based assay system (Supporting Information, Figure S3).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Evaluation of Amyloid β Derived and Amyloid β Independent Enhancers of the Peroxidase-like Activity of Heme

et al. 2016

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Labile heme has been suggested to have an impact in several severe diseases. In the context of Alzheimer's disease (AD), however, decreased levels of free heme have been reported. Therefore, we were looking for an assay system that can be used for heme concentration determination. From a biochemical point of view the peroxidase activity of the Aβ-heme complex seemed quite attractive to pursue this goal. As a consequence, a peptide that is able to increase the readout even in the case of a low heme concentration is favorable. The examination of Aβ- and non-Aβ-derived peptides in complex with heme revealed that the peroxidase-like activity significantly depends on the peptide sequence and length. A 23mer His-based peptide derived from human fatty acyl-CoA reductase 1 in complex with heme exhibited a significantly higher peroxidase activity than Aβ(40)-heme. Structural modeling of both complexes demonstrated that heme binding via a histidine can be supported by hydrogen bond interactions of a basic residue near the propionate carboxyl function of protoporphyrin IX. Furthermore, the interplay of Aβ-heme and the lipoprotein LDL as a potential physiological effector of Aβ was examined.

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Heme-peptide complexes as peroxidase models

Cited by 20 publications

References 55 publications

Induction of Enzyme-like Peroxidase Activity in an Iron Porphyrin Complex Using Second Sphere Interactions

Induction of Enzyme-like Peroxidase Activity in an Iron Porphyrin Complex Using Second Sphere Interactions

Heme Binding Induces Dimerization and Nitration of Truncated β‐Amyloid Peptide Aβ16 Under Oxidative Stress

Synthesis and Evaluation of Amyloid β Derived and Amyloid β Independent Enhancers of the Peroxidase-like Activity of Heme

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