Sequence‐Specific Oxidative Degradation of Tripeptides by a Cobalt( III ) Complex Containing a Terpyridine Ligand

A sequence‐specific oxidative degradation of an oligopeptide consisting of aliphatic amino acids was performed with a ternary cobalt( III ) complex. Under aerobic conditions the reaction of [Co(CO 3 )(OH)(terpy)] and an equimolar amount of tripeptide at 40 °C at pH 8.5 gave two fraction bands ( a and b ) with water and then two bands ( c and d ) with NaCl solution, respectively, after column separation. In the case of gly‐gly‐leu (ggl, 1 ), [Co(gg′l)(terpy)] [ 1a , gg′l = glycyl(2‐oxoglycyl)leucine], [Co(g′l)(terpy)] [ 1b , g′l = N ‐(2‐oxoglycyl)leucine], [Co(ggl)(terpy)] + ( 1c ), and [Co(terpy) 2 ] 3+ ( 1d ) were obtained. The crystal structure of 1c , which was the main product, revealed that the starting ggl ligand was cleaved to give a bis‐amide compound, g′l, which might be generated by loss of N‐terminal glycine and carbonylation of the α‐carbon of the N‐2 glycine residue. Although the source of the oxygen of the newly generated carbonyl group is not clear, gg′l is supposed to be an intermediate for g′l on the basis of time‐dependent HPLC analyses. NMR investigation of other tripeptides [βala‐gly‐leu ( 2 ), gly‐gly‐phe ( 3 ), and gly‐gly‐ala ( 4 )] containing a bulky C‐terminal aliphatic side chain indicated the formation of the corresponding oxidation complexes. On the other hand, peptides containing a C‐terminal glycine residue [gly‐gly‐gly ( 5 ) and phe‐gly‐gly ( 6 )] or an N‐2 β‐alanine residue [gly‐βala‐leu ( 7 )] did not give such a transformation product. The crystal structure of [Co(fgg)(terpy)] ( 6c ) revealed that the tripeptide is coordinated to cobalt with a tridentate N‐terminal N ‐ N ‐ N geometry. Such sequence specificity demonstrated in the reaction of the aliphatic tripeptide complexes is interpreted by the interligand interaction between the side chain of the C‐terminal amino acid residue and terpy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)