A Novel Binuclear Pd(II) Complex Displaying the Synergic Peptide Cleavage Behaviour
Mononuclear Pd(II) complexes with two leaving groups are able to promote His-, Cys- and Met-orientated peptide hydrolysis, and exploring the peptide cleavage behavior of novel Pd(II) complex may provide “Omics” studies promising artificial protease. In this study, a novel binuclear Pd(II) complex [Pd2(-O-L-H)(-Cl)](ClO4)2 (L=2,6-bis(N-2'-aminoethylaminomethyl)-p-cresol) was constructed to promote peptide hydrolysis. Although each Pd(II) center has only one leaving group (Cl) in this complex, electrophoresis and LC-MS-MS determination discloses that this complex enables myoglobin cleavage on the second upstream peptide bond from His and Met. Study on peptide celavage confirms also the His- and Met-orientated peptide hydrolysis, yet no Cys-orientated hydrolysis was observed, although the cysteine-induced peptide/complex binding is distinct. Cysteine in peptide even prevents the complex from His-orientated hydrolysis, and oxidizing cysteine residue recovers the His-orientated hydrolysis. This peptide cleavage behavior is quite different from the simultaneous His-, Cys-, and Met-orientated hydrolysis promoted by mononuclear Pd(II) complex. Theoretic study suggests that the two Pd(II) centers of this complex might promote His- and Met-orientated hydrolysis in a synergic manner: one Pd(II) center binds selectively on peptide or protein, and the other coordinates with amide bond and water favoring nucleophilic attack to peptide bond. The thiol group of cysteine is inclined to bridge the two Pd(II) centers to form a “closed” sulphur-bridge structure, disfavoring the Cys-orientated hydrolysis. This study not only demonstrats the peptide cleavage behavior of this binuclear Pd(II) complex, but also provides a polynuclear strategy to regulate the peptide cleavage behavior of Pd(II) complexes.