His-oriented peptide hydrolysis promoted by cis-[Pt(en)(H2O)2]2+: a new specific peptide cleavage site.

The new specific hydrolysis of histidine-containing peptides promoted by cis-[Pt(en)(H(2)O)(2)](2+) was investigated by electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance spectrometry (NMR). MS determination demonstrated that cis-[Pt(en)(H(2)O)(2)](2+) anchors to AcGHG with the stoichiometry of either 1:1 or 2:1 (Pt/peptide), but only with 1:1 stoichoimetry to AcGHL. Cis-[Pt(en)(H(2)O)(2)](2+) is able to promote the cleavage of the first downstream peptide bond from histidine at 60 degrees C and pH 2.65, and Pt-anchored peptides are the essential intermediates for the promoted hydrolysis. Moreover, the larger amount of Pt(II) complex results in higher fragmental yield and higher hydrolysis rate. In the presence of 1 equiv of Pt(II) complex, (1)H NMR determination confirmed the apparent first-order kinetics of the Pt(II)-promoted hydrolysis and the hydrolysis rate for AcGHG and AcGHL is 0.20 day(-1) and 0.14 day(-1), respectively. Moreover, Pt(II) coordinating to histidine imidazole is the key step to form the Pt(II)-anchored peptides. The Pt(II)-activating the first His-downstream carbonyl group via synergic coordinating to His imidazole and carbonyl O atom has been proposed for the Pt(II)-promoted his-oriented peptide hydrolysis. The lower rate for AcGHL should be correlated to the steric hindrance of Leu side chain to the second Pt(II) coordinating to tripeptide. In addition, the newly confirmed specific His-oriented peptide cleavage site implies a new potential strategy for target cleavage of peptides or proteins.