Naslov
Biomimetic modelling of a mononuclear metallopeptidases active site with the triazole based tridentate ligands

Autori
Višnjevac, Aleksandar ; Perdih, Franc ; Požgan, Franc ; Štefane, Bogdan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
22 Croatian-Slovenian Crystallographic Meeting, BOA / Ppović, Stanko ; Cetina, Mario ; Štefanić, Zoran - Zagreb : Hrvatska kristalografska zajednica HAZU, 2013, 9-9

Skup
22. Croatian-Slovenian Crystallographic Meeting

Mjesto i datum
Biograd na Moru, Hrvatska, 12.06.2013. - 16.06.2013

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
biomimetic modelling; zinc; cobal; nickel; triazoles

Sažetak
The most common structural motif in the active site of mononuclear metallopeptidases is a tetrahedral zinc centre attached to the protein backbone by three amino acid residues, with the fourth coordination site being occupied by a catalytically essential water/hydroxyde, to be replaced by a substrate during the catalysis. Histidine is the most common amino acid to bind zinc in this type of active site, but Glu, Asp and Cys are also frequently encountered. We designed and prepared two tridentate NNN-type ligands, derivatives of (1H-1, 2, 3-triazolyl)amine, as well as their Zn(II) complexes, as biomimetic models of metallopeptidase active site with the trihystidine coordination core. In Zn(II) complex 2, tridentate NNN-type ligand 1 with the aliphatic side chain, acts as a bidentate NN type ligand, refusing to bind the metal cation via its triazole N2 nitrogen. Complex 2 crystallizes in triclinic P-1 space group with two molecules per units cell. The tetrahedral coordination sphere around the Zn(II) is formed by two nitrogen atoms from the ligand side chain, and two chlorine counteranions. Tridentate NNN-type ligand 3, a bis-pyridine derivative of 1, on the other hand, readily binds the zinc cation in a tridentate manner (complex 4). This results with a complex with a slightly distorted trigonal bipyramide around the central Zn(II) ion, where the coordination sphere is composed of three nitrogen atoms from the ligand 3 (including both pyridine N atoms) and two chlorine counteranions. Ligand 5, a monopyridine derivative of 1, readily binds Ni(II) in a tridentate NNN fashion, forming the Ni(II) complex 6, where the coordination sphere includes the triazole N2. The octahedral coordination sphere is completed by two nitrogens form the ligand side chain, the chlorid anions and an oxygen from the solvent molecule. Complexes 4 and 6 are suitable biomimetic structural models of the metallopeptidase active site. These complexes will be tested for their catallytic activity on hydrolysis of peptide bond in suitable model substrates.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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