REGIOSELECTIVE CLEAVAGE BY A PALLADIUM(II) AQUA COMPLEX OF A POLYPEPTIDE IN DIFFERENT OVERALL CONFORMATIONS

Two molecules of the complex cis-[Pd(en)(H2O)(2)](2+) lose aqua ligand s and bind to His5 and His9 residues in the nonadecapeptide that is th e carboxy-terminal segment of the protein myohemerythrin. The known mo des of palladium(II)-histidine coordination are detected by H-1 NMR sp ectroscopy. Only the [Pd(en)(H2O)](2+) group bound to His5 cleaves the polypeptide backbone; the group bound to His9 does not. Only the amid e bond Val3-Pro4 is cleaved. This regioselectivity is attributed to el ectrostatic repulsion of the [Pd(en)(H2O)](2+) group by cationic lysin e residues 6, 7, and 10 and the absence of repulsion by the residues ' 'upstream'' from His5. The polypeptide in a partially alpha-helical co nformation and the tripeptide AcGly-Gly-His, which adopts many flexibl e conformations, are both cleaved at the second amide bond ''upstream' ' from the histidine residue bearing the [Pd(en)(H2O)](2+) group. More over, the rate constants for the cleavages of these two peptides are v irtually the same. Regioselectivity and kinetics of the cleavage of pe ptides by palladium(II) aqua complexes seems to be affected by the loc al secondary structure in the vicinity of the scissile bond. This stud y is a step toward our ultimate goal-design of artificial metallopepti dases.