1H N.M.R. investigations of the selective intramolecular migration of a platinum(II) complex from methionine sulfur to imidazole N 1 in N-acetylated L-methionyl-L-histidine

Abstract

Reactions of two platinum(II) complexes [Pt(dien)Cl]+ and [Pt(Gly-Met-S,N,N´)Cl], in which dien is diethylenetriamine and Gly-Met is the dipeptide glycyl-L-methionine coordinated through the sulfur and two nitrogen atoms, with N-acetylated dipeptide L-methionyl-L-histidine (MeCO-Met-His) have been studied by 1H n.m.r. spectroscopy. All reactions were carried out in 50 mM phosphate buffer at pD 7.4 and at room temperature. In the initial stages of the reactions both platinum(II) complexes form a kinetically favoured platinum–peptide complex with unidentate coordination of MeCO-Met-His through the sulfur atom of the methionine residue. In the second stages of the reaction an intramolecular migration of a [Pt(dien)]2+ unit from the sulfur to the nitrogen atom of imidazole has been observed. This migration reaction is very slow and strongly selective to the N 1 atom of the imidazole ring of the histidine side chain. No migration of the platinum(II) complex was observed in the reaction between [Pt(Gly-Met-S,N,N´)Cl] and the dipeptide MeCO-Met-His. It was found that the latter complex, with a more sterically hindered Gly-Met ligand, reacts more slowly with thioether-containing molecules than [Pt(dien)Cl]+ and forms a more stable platinum–sulfur bond. This study is an important step in the development of new platinum(II) complexes for selective covalent modification of peptides and proteins.

Reactions of Platinum II Complexes with Sulfur- and Nitrogen-Containing Biomolecules: Selective Intermolecular Migration of the Thioether-Bound Platinum II Complex to the N7 Nitrogen Atom of Guanosine-5’-Monophosphate

“…The above-mentioned findings are in accordance to those previously reported for the selective intramolecular migration of [Pt(dien)Cl] + complex (dien is diethylenetriamine) from the methionine sulfur to the imidazole N1 atom of the N-acetylated L-methionyl-L-histidine (Ac-LMet-His) (8), as well as to the N7 nitrogen atom of guanosine-5'-monophosphate (14). Also, it was found that this migration reaction is very slow and strongly selective to the N1 atom of the imidazole ring of the histidine side chain.…”

“…Also, it was found that this migration reaction is very slow and strongly selective to the N1 atom of the imidazole ring of the histidine side chain. On the other hand, no migration of the Pt(II) complex was observed in the reaction between [Pt(Gly-L-Met-S,N,N') Cl] and Ac-L-Met-His dipeptide (8). It was explained by the fact that this complex, with a more sterically hindered Gly-L-Met ligand dipeptide, reacts more slowly with thioethercontaining molecules than other two Pt(II) complexes and forms a more stable Pt(II)-sulfur bond (Table 1) (7,8,15) .…”

“…The monofunctional [PtCl(dien)] + complex, with the dien (dien is 1,5-diamino-3-azapentane) acting as a non-removable tridentate ligand, has been shown to be a very useful model for the study of the kinetics and mechanism of the interactions of Pt(II) antitumor complexes with nitrogen-and sulfur-containing biomolecules. Results obtained by the NMR investigation of the competitive binding of the L-methionine (L-Met), N-acetylated dipeptide glycyl-L-methionine (Ac-Gly-LMet) and guanosine-5'-monophosphate (5'-GMP) to the monofunctional [PtCl(dien)] + complex have shown that 5'-GMP selectively displaces Pt-S-Met bound (7,8)…”

The Copper Transporter CTR1 Regulates Cisplatin Uptake in Saccharomyces cerevisiae

“…DDP is also known to bind to both methionine and histidine in a variety of contexts (Djuran and Milinkovic, 2000, and references therein). Recent studies indicate that the bond linking DDP to the sulfur in methionine is labile enough to permit transfer of the DDP to histidine (van Boom et al, 1999;Djuran and Milinkovic, 2000), suggesting the feasibility of sequential chelation and transport steps similar to those of copper. Although the Cu(I) ion in water can exist in a tetrahedral structure, copper forms a square planar structure similar to that of DDP when coordinated by four amino groups (Theophanides and Anastassopoulou, 2002).…”

Hidroliza peptida koji sadrze L-metionin i L-histidin pomocu razlicitih kompleksa paladijuma(II) i platine(II)

“…На основу добијених резултата у овом раду, као и раније објављених резултата[130][131][132][133], може се закључити да се реакција интрамолекулске миграције Pt(II) комплекса са сумпора тиоетарског лиганда на атом азота имидазоловог прстена хистидина може одвијати при физиолошким условима. У реакцијама [Pt(dien)Cl] + са His дипептидом је знатно бржа при чему долази до скоро потпуне координације N3 атома азота хистидинског остатка за Pt(II) комплекс (Слика 44).…”