simple method to obtain branched peptides consists of binding a well-defined number of peptide sequences to a central scaffold. Molecules of this type have been synthesized in the past and have been investigated as new anticancer drugs, vaccines and antibacterial agents [1]. In this way, if the peptides used to build up these structures have binding properties towards metal ions, it is possible to obtain completely new polydentate peptide ligands, with the ability to mimic the coordination sites of natural metalloenzymes. In this context, the present contribution reports the results of a pilot study in which: first of all, the two oligopeptides AAHAWG-NH2 (P1) and HAWG-NH2 (P2), protected at their carboxylic terminus, were synthesized and studied as ligands of Cu(II) and Zn(II); secondly, the corresponding tetrameric branched forms were synthesized and investigated. The latter were obtained by binding four identical peptides, of one of the two kinds, to a cyclam platform, through a cysteine-maleimide bridge (Scheme 1) [2]. While the binding behaviour of P1 and P2 towards the considered metal ions is perfectly in line with what already known in the literature for oligopeptides that contain a histidine residue in position 3 (ATCUN-type) or 1 (histamine-like) [3,4], in the case of tetrameric structures, peculiar behaviours are observed. In fact, the branched peptides contain four imidazole residues which are blocked, through a spacer, to a single cyclam platform, resulting very close each other and thus producing a very high local concentration of the donor atoms. References: [1] Pini, A.; Falciani, C.; Bracci, L., Branched Peptides as Therapeutics. Curr. Protein Pept.Sci.2008, 9, 468-477. [2] Guerrini, R.; Marzola, E.; Trapella, C.; Pelà, M.; Molinari, S.; Cerlesi, M. C.; Malfacini, D.; Rizzi, A.; Salvadori, S.; Calò, G.; A novel and facile synthesis of tetra branched derivatives of nociceptin/orphanin FQ. Bioorg. Med. Chem.2014, 22, 3703–3712. [3] Zamariola G.; Watly J.; Gallerani E.; Gavioli R.; Guerrini R.; Kozlowski H.; Remelli M.; AGHLDDLPGALSAL: a hemoglobin fragment potentially competing with albumin to bind transition metal ions. J. Inorg. Biochem.2016, 163, 301-310. [4] Remelli, M.; Conato, C.; Agarossi, A.; Pulidori, F.; Młynarz, P.; Kozłowski, H.; Copper complexes of dipeptides with l-Lys as C-terminal residue: a thermodynamic and spectroscopic study. Polyhedron2000, 19, 2409–2419.

Macrochelates from rigid polypeptides: a step forward towards synthetic enzymes?

Maurizio REMELLI;Remo GUERRINI;Nicola MARCHETTI;Denise BELLOTTI;
2018

Abstract

simple method to obtain branched peptides consists of binding a well-defined number of peptide sequences to a central scaffold. Molecules of this type have been synthesized in the past and have been investigated as new anticancer drugs, vaccines and antibacterial agents [1]. In this way, if the peptides used to build up these structures have binding properties towards metal ions, it is possible to obtain completely new polydentate peptide ligands, with the ability to mimic the coordination sites of natural metalloenzymes. In this context, the present contribution reports the results of a pilot study in which: first of all, the two oligopeptides AAHAWG-NH2 (P1) and HAWG-NH2 (P2), protected at their carboxylic terminus, were synthesized and studied as ligands of Cu(II) and Zn(II); secondly, the corresponding tetrameric branched forms were synthesized and investigated. The latter were obtained by binding four identical peptides, of one of the two kinds, to a cyclam platform, through a cysteine-maleimide bridge (Scheme 1) [2]. While the binding behaviour of P1 and P2 towards the considered metal ions is perfectly in line with what already known in the literature for oligopeptides that contain a histidine residue in position 3 (ATCUN-type) or 1 (histamine-like) [3,4], in the case of tetrameric structures, peculiar behaviours are observed. In fact, the branched peptides contain four imidazole residues which are blocked, through a spacer, to a single cyclam platform, resulting very close each other and thus producing a very high local concentration of the donor atoms. References: [1] Pini, A.; Falciani, C.; Bracci, L., Branched Peptides as Therapeutics. Curr. Protein Pept.Sci.2008, 9, 468-477. [2] Guerrini, R.; Marzola, E.; Trapella, C.; Pelà, M.; Molinari, S.; Cerlesi, M. C.; Malfacini, D.; Rizzi, A.; Salvadori, S.; Calò, G.; A novel and facile synthesis of tetra branched derivatives of nociceptin/orphanin FQ. Bioorg. Med. Chem.2014, 22, 3703–3712. [3] Zamariola G.; Watly J.; Gallerani E.; Gavioli R.; Guerrini R.; Kozlowski H.; Remelli M.; AGHLDDLPGALSAL: a hemoglobin fragment potentially competing with albumin to bind transition metal ions. J. Inorg. Biochem.2016, 163, 301-310. [4] Remelli, M.; Conato, C.; Agarossi, A.; Pulidori, F.; Młynarz, P.; Kozłowski, H.; Copper complexes of dipeptides with l-Lys as C-terminal residue: a thermodynamic and spectroscopic study. Polyhedron2000, 19, 2409–2419.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2480157
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