Triggering Cu-coordination change in Cu(<scp>ii</scp>)-Ala-His-His by external ligands

González, Paulina; Bossak-Ahmad, Karolina; Vileno, Bertrand; Wezynfeld, Nina E.; Khoury, Youssef El; Hellwig, Petra; Hureau, Christelle; Bal, Wojciech; Faller, Peter

doi:10.1039/c9cc03174j

Cited by 17 publications

(19 citation statements)

References 28 publications

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“…Both complexes Cu II (Aβ 4–16 ) and Cu II (Aβ 11–16 ) display a classical EPR signal for a 4 N coordination, with superhyperfine lines in the perpendicular region indicative of N equatorial ligands (Figure S2 (b) and (d)) and reminiscent of Cu II bound in a ATCUN [7b, 24] motif including those obtained with Aβ 11–15 and Aβ 4–16 [13, 14, 25] . This signature strongly differs from that of Cu II (Aβ 1–16 ) (Figure S2 (a)), allowing the removal of Cu II from Cu II (Aβ 1–16 ) by the two N ‐truncated peptides to be easily monitored.…”

Section: Resultsmentioning

confidence: 91%

Impact of N‐Truncated Aβ Peptides on Cu‐ and Cu(Aβ)‐Generated ROS: Cu^I Matters!

Esmieu

Ferrand

Borghesani

et al. 2020

Chemistry A European J

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In vitro Cu(Aβ1–x)‐induced ROS production has been extensively studied. Conversely, the ability of N‐truncated isoforms of Aβ to alter the Cu‐induced ROS production has been overlooked, even though they are main constituents of amyloid plaques found in the human brain. N‐Truncated peptides at the positions 4 and 11 (Aβ4–x and Aβ11–x) contain an amino‐terminal copper and nickel (ATCUN) binding motif (H2N‐Xxx‐Zzz‐His) that confer them different coordination sites and higher affinities for CuII compared to the Aβ1–x peptide. It has further been proposed that the role of Aβ4–x peptide is to quench CuII toxicity in the brain. However, the role of CuI coordination has not been investigated to date. In contrast to CuII, CuI coordination is expected to be the same for N‐truncated and N‐intact peptides. Herein, we report in‐depth characterizations and ROS production studies of Cu (CuI and CuII) complexes of the Aβ4–16 and Aβ11–16 N‐truncated peptides. Our findings show that the N‐truncated peptides do produce ROS when CuI is present in the medium, albeit to a lesser extent than the unmodified counterpart. In addition, when used as competitor ligands (i.e., in the presence of Aβ1–16), the N‐truncated peptides are not able to fully preclude Cu(Aβ1–16)‐induced ROS production.

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Section: Resultsmentioning

confidence: 91%

Impact of N‐Truncated Aβ Peptides on Cu‐ and Cu(Aβ)‐Generated ROS: Cu^I Matters!

Esmieu

Ferrand

Borghesani

et al. 2020

Chemistry A European J

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“…Imidazole-based ligands can increase the overall affinity of metal complexes containing tridentate ligands by several orders of magnitude [ 20 , 29 , 30 , 31 , 32 , 33 ]. Urocanic acid, a by-product of L-histidine, contains an imidazole ring that could form a stable ternary Cu(II) complex with GHK in a manner similar to other Xaa-His peptides such as Trp–His–Trp–Ser–Lys–Asn–Arg, Gly–His–Thr–Asp, and Ala–His–His [ 20 , 21 , 34 ].…”

Section: Resultsmentioning

confidence: 99%

Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate

Bossak-Ahmad

Wiśniewska

Bal

et al. 2020

IJMS

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The tripeptide NH2–Gly–His–Lys–COOH (GHK), cis-urocanic acid (cis-UCA) and Cu(II) ions are physiological constituents of the human body and they co-occur (e.g., in the skin and the plasma). While GHK is known as Cu(II)-binding molecule, we found that urocanic acid also coordinates Cu(II) ions. Furthermore, both ligands create ternary Cu(II) complex being probably physiologically functional species. Regarding the natural concentrations of the studied molecules in some human tissues, together with the affinities reported here, we conclude that the ternary complex [GHK][Cu(II)][cis-urocanic acid] may be partly responsible for biological effects of GHK and urocanic acid described in the literature.

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“…protein, amino acid, ions etc) that leads to a higher stability or bind a substrate (e.g. reducing agent) [33][34][35]. Second, while its affinity for Cu(II) is almost as high as for XZH at pH 7.4, it becomes stronger than XZH when lowering the pH.…”

Section: Introductionmentioning

confidence: 99%

Copper-binding motifs Xxx-His or Xxx-Zzz-His (ATCUN) linked to an antimicrobial peptide: Cu-binding, antimicrobial activity and ROS production

Bouraguba

Glattard

Naudé

et al. 2020

Journal of Inorganic Biochemistry

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Depending on the coordination, copper ions can have a very high activity in catalyzing the production of reactive oxygen species. Thus interest arose in increasing the activity of antimicrobial peptides (AMPs) by equipping them with a Cu-binding unit. Several examples, native and engineered, have been investigated with the motif Xxx-Zzz-His, called Amino Terminal Cu(II)-and Ni(II)-binding (ATCUN) motif. Here we investigate a short AMP that was equipped either with Xxx-Zzz-His or Xxx-His. Xxx-His is a shorter motif and yields a more redox active copper complex. The control AMP, Xxx-His-AMP and Xxx-Zzz-His-AMP were investigated toward Cu-binding, Reactive Oxygen Species (ROS) production and antimicrobial activity in E. coli. The data indicate that these Cu-binding motifs have very limited impact on antimicrobial activity and low ROS production capability.

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Triggering Cu-coordination change in Cu(ii)-Ala-His-His by external ligands

Abstract: A switch in copper(ii)-coordination between the two motifs Xxx-Zzz-His (ATCUN) and Xxx-His in the hybride peptide Ala-His-His is induced by adding a ligand such as imidazole.

Cited by 17 publications

References 28 publications

Impact of N‐Truncated Aβ Peptides on Cu‐ and Cu(Aβ)‐Generated ROS: Cu^I Matters!

Impact of N‐Truncated Aβ Peptides on Cu‐ and Cu(Aβ)‐Generated ROS: Cu^I Matters!

Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate

Copper-binding motifs Xxx-His or Xxx-Zzz-His (ATCUN) linked to an antimicrobial peptide: Cu-binding, antimicrobial activity and ROS production

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Triggering Cu-coordination change in Cu(ii)-Ala-His-His by external ligands

Abstract: A switch in copper(ii)-coordination between the two motifs Xxx-Zzz-His (ATCUN) and Xxx-His in the hybride peptide Ala-His-His is induced by adding a ligand such as imidazole.

Cited by 17 publications

References 28 publications

Impact of N‐Truncated Aβ Peptides on Cu‐ and Cu(Aβ)‐Generated ROS: CuI Matters!

Impact of N‐Truncated Aβ Peptides on Cu‐ and Cu(Aβ)‐Generated ROS: CuI Matters!

Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate

Copper-binding motifs Xxx-His or Xxx-Zzz-His (ATCUN) linked to an antimicrobial peptide: Cu-binding, antimicrobial activity and ROS production

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Impact of N‐Truncated Aβ Peptides on Cu‐ and Cu(Aβ)‐Generated ROS: Cu^I Matters!

Impact of N‐Truncated Aβ Peptides on Cu‐ and Cu(Aβ)‐Generated ROS: Cu^I Matters!