The two branched peptides (AAHAWG)4-PWT2 and (HAWG)4-PWT2 where synthesized by mounting linear peptides on a cyclam-based scaffold (PWT2), provided with four maleimide chains, through a thio-Michael reaction. The purpose of this study was primarily to verify if the two branched ligands had a Cu(II) coordination behavior reproducing that of the single-chain peptides, namely AAHAWG-NH2, which bears an Amino Terminal Cu(II)- and Ni(II)-Binding (ATCUN) Motif, and HAWG-NH2, which presents a His residue as the N-terminal amino acid, in a wide pH range. The study of Cu(II) binding was performed by potentiometric, spectroscopic (UV–vis absorption, CD, fluorescence) and ESI-MS techniques. ATCUN-type ligands ((AAHAWG)4-PWT2 and AAHAWG-NH2) were confirmed to bind one Cu(II) per peptide fragment at both pH 7.4 and pH 9.0, with a [NH2, 2N−, NIm] coordination mode. On the other hand, the ligand HAWG-NH2 forms a [CuL2]2+ species at neutral pH, while, at pH 9, the formation of 1:2 Cu(II):ligand adducts is prevented by amidic nitrogen deprotonation and coordination, to give rise solely to 1:1 species. Conversely, Cu(II) binding to (HAWG)4-PWT2 resulted in the formation of 1:2 copper:peptide chain also at pH 9: hence, through the latter branched peptide we obtained, at alkaline pH, the stabilization of a specific Cu(II) coordination mode which results unachievable using the corresponding single-chain peptide. This behavior could be explained in terms of high local peptide concentration on the basis of the speciation of the Cu(II)/single-chain peptide systems.

Cu(II) coordination to His-containing linear peptides and related branched ones: Equalities and diversities

Guerrini, Remo
Secondo
;
Albanese, Valentina;Marchetti, Nicola;Bellotti, Denise;Remelli, Maurizio
Ultimo
2020

Abstract

The two branched peptides (AAHAWG)4-PWT2 and (HAWG)4-PWT2 where synthesized by mounting linear peptides on a cyclam-based scaffold (PWT2), provided with four maleimide chains, through a thio-Michael reaction. The purpose of this study was primarily to verify if the two branched ligands had a Cu(II) coordination behavior reproducing that of the single-chain peptides, namely AAHAWG-NH2, which bears an Amino Terminal Cu(II)- and Ni(II)-Binding (ATCUN) Motif, and HAWG-NH2, which presents a His residue as the N-terminal amino acid, in a wide pH range. The study of Cu(II) binding was performed by potentiometric, spectroscopic (UV–vis absorption, CD, fluorescence) and ESI-MS techniques. ATCUN-type ligands ((AAHAWG)4-PWT2 and AAHAWG-NH2) were confirmed to bind one Cu(II) per peptide fragment at both pH 7.4 and pH 9.0, with a [NH2, 2N−, NIm] coordination mode. On the other hand, the ligand HAWG-NH2 forms a [CuL2]2+ species at neutral pH, while, at pH 9, the formation of 1:2 Cu(II):ligand adducts is prevented by amidic nitrogen deprotonation and coordination, to give rise solely to 1:1 species. Conversely, Cu(II) binding to (HAWG)4-PWT2 resulted in the formation of 1:2 copper:peptide chain also at pH 9: hence, through the latter branched peptide we obtained, at alkaline pH, the stabilization of a specific Cu(II) coordination mode which results unachievable using the corresponding single-chain peptide. This behavior could be explained in terms of high local peptide concentration on the basis of the speciation of the Cu(II)/single-chain peptide systems.
Perinelli, Monica; Guerrini, Remo; Albanese, Valentina; Marchetti, Nicola; Bellotti, Denise; Gentili, Silvia; Tegoni, Matteo; Remelli, Maurizio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2413418
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