Interaction of molybdocene dichloride with cysteine-containing peptides: coordination, regioselective hydrolysis, and intramolecular aminolysis.
Reactions of the organometallic compound molybdocene dichloride (Cp2MoCl2, Cp = eta5-cyclopentadienyl) with the cysteine-containing peptides L-cysteinylglycine (Cys-Gly), N-acetyl-L-cysteine (AcCys), glycyl-L-cysteine (Gly-Cys), glycyl-L-cysteinylglycine (Gly-Cys-Gly), and gamma-L-glutamyl-L-cysteinylglycine (glutathione, GSH) have been studied in aqueous solution in the pH range 2-9. The dipeptides Cys-Gly and Gly-Cys and the acetylated amino acid AcCys form 1:1 and 2:1 complexes of composition [Cp2Mo(peptide-S)(OH(2))]n+/- and [Cp2Mo(peptide-S)2]n+/- as well as the chelates [Cp2Mo(AcCys-S,O)], [Cp2Mo(Gly-Cys-S,O)]+, and [Cp2Mo(Cys-Gly-S,N)] with the Cp2Mo2+ unit binding to the deprotonated thiolate group and the free amino or carboxylate group of the cysteine residue. Upon treatment of Gly-Cys-Gly and the naturally occurring tripeptide GSH with Cp2MoCl2 at elevated temperature, release of free glycine was observed. The Cp2Mo2+ entity coordinates to the thiolate group of GSH and mediates regioselective hydrolysis of the Cys-Gly peptide bond by intramolecular metal hydroxide activation. Cp2Mo2+-promoted hydrolysis of GSH was followed at pD 7.4 and 5.2 and 40 and 60 degrees C. By contrast, the Cys-Gly bond in [Cp2Mo(Gly-Cys-Gly-S,N)] is cleaved by intramolecular aminolysis at pD > or = 7.4 and 60 degrees C leading to glycine and the Cp2Mo2+ complex of the 2,5-diketopiperazine derivative cyclo-(Gly-Cys). Chelating coordination of the Cp2Mo2+ moiety to the thiolate group and to the deprotonated amide nitrogen of the tripeptide changes the configuration of the peptide bond from (preferred) trans to cis, thus enabling nucleophilic attack of the primary amino group at the Cys-Gly bond. The reaction product [Cp2Mo{cyclo-(Gly-Cys)}] x 2H2O has been characterized by X-ray crystallography.
Erxleben
Andrea
A
Fachbereich Chemie, Universität Dortmund, Otto-Hahn-Strasse 6, 44221 Dortmund, Germany. Andrea.Erxleben@uni-dortmund.de
D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D001665:Binding Sites; D002614:Chelating Agents / Q000737:chemistry; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000378:metabolism*; D054659:Diketopiperazines; D004151:Dipeptides / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008667:Metalloproteins / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry; D009942:Organometallic Compounds / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010879:Piperazines / Q000737:chemistry; D013237:Stereoisomerism; D013696:Temperature
D000577:Amides; D000588:Amines; D002614:Chelating Agents; D054659:Diketopiperazines; D004151:Dipeptides; D008667:Metalloproteins; D009942:Organometallic Compounds; D010455:Peptides; D010879:Piperazines; C024389:molybdocene dichloride; C028505:cysteinylglycine; D005978:Glutathione; D003545:Cysteine; D009584:Nitrogen