Solution conformation and hydrolytic activity of cyclo(D‐leu‐L‐His)

Abstract

AbstractIt has been reported previously that a cyclic dipeptide, cyclo(D‐Leu‐L‐His), showed a high hydrolytic activity toward a hydrophobic ester, p‐nitrophenyl laurate. In order to determine the reason for the high catalytic activity, the conformation of cyclo(D‐Leu‐L‐His) in aqueous solution was investigated by nuclear magnetic resonance and circular dichroism spectroscopy and compared with the conformation of cyclo(L‐Leu‐L‐His), which was nearly inactive in otherwise the same conditions for the hydrolysis. It was demonstrated that the spatial arrangement of the hydrophobic isobutyl group of the D‐leucyl residue and of the nucleophilic imidazolyl group of the L‐histidyl residue in cyclo(D‐Leu‐L‐His) matches very well with the long acyl chain and the active ester function of p‐nitrophenyl laurate. On the other hand, in cyclo(L‐Leu‐L‐His) the hydrophobic and the nucleophilic pendant groups are too close with each other to cooperate intramolecularly for the hydrolysis. It was concluded that the different steric structures of the diastereomers can explain the large difference of the catalytic activities.