Zinc mediated methyl transfer from trimethyl phosphate to chelating and non-chelating alkyl thiols. Model for Zn-dependent methyltransferases.
The methyl transfer from trimethyl phosphate to alkyl thiols was investigated in the presence of zinc ions and in the absence of strong base. The chelating thiol N-(2-mercaptoethyl)picolylamine (MEPAH) was methylated by trimethyl phosphate, in MeOH, in the presence of Zn salts whereas the reaction did not take place in the absence of Zn(2+). The pre-formed complex (MEPA)(2)Zn was methylated faster than the MEPAH in the presence of zinc ions The methyl transfer also took place in chloroform with similar yields at room temperature. When non-chelating hexanethiol was the methyl acceptor, a slower reaction took place in the presence of pyridine which was independent of Zn(2+). Kinetic studies of the methyl transfer from trimethyl phosphate to (MEPA)(2)Zn gave a second-order rate constant of 5.0 x 10(-5) M(-1) s(-1) as measured by 1H NMR spectroscopy in MeOH. The results obtained suggest that the methyl transfer to MEPA-Zn involves a zinc-bound thiolate.
Machuqueiro
Miguel
M
Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012, Bern, Switzerland.
Darbre
Tamis
T
D002614:Chelating Agents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008780:Methyltransferases / Q000737:chemistry*; D008956:Models, Chemical; D010755:Organophosphates / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
D002614:Chelating Agents; D010755:Organophosphates; D013438:Sulfhydryl Compounds; D008780:Methyltransferases; D015032:Zinc; C003715:trimethyl phosphate