3-DIMENSIONAL STRUCTURE OF AL3-CONTAINING PEPTIDES BY NMR AND MOLECULAR MODELING STUDY - COMPLEXATION OF A THYMIC HORMONE()

The biological coordination chemistry of aluminum has received only li mited attention until the last decade. To this end, the interaction be tween aluminum and thymulin, a linear nonapeptide of thymic origin iso lated from serum, was investigated by using high resolution NMR spectr oscopy. These experiments were performed in two different solvents, na mely DMSO-d(6) and the so-called cryoprotective mixture (water+DMSO), i.e. a mixture that resembles water in many properties. NMR data analy sis indicates the existence of one type of complex with a 1:2 stoichio metry, associating two peptide molecules and one Al3+ cation. In this complex the Asn(9) carboxylate C-terminal group and the Ser(4) hydroxy l group are ligated to the metal. The three-dimensional structure of t he 1:2 Al3+-thymulin complex was determined by distance geometry calcu lations and restrained molecular dynamics simulations. Distance geomet ry calculations were performed with the Biosym DG II program using the NOE interproton distances as constraints. Further structural analysis was carried out by restrained molecular dynamics calculations with th e Biosym DISCOVER program.