First evidence on induced topological changes in supercoiled DNA by an aluminium D-aspartate complex

Abstract

Aluminium is a debatable and suspected etiological factor in neurodegenerative disorders. Aluminium-amino acid complexes also play an important role in the complex biology of the metal. Recent reports indicate the presence of D-aspartate and D-glutamate in aging brain, human breast tumors, core amyloid plaques and neurofibrillary tangles of Alzheimer's brain. This stereoinversion from the L- to the D-enantiomer is enhanced by Al. Further, the observation that Al is localized in the chromatin region encouraged the present study of the interaction of Al-amino acid complexes with DNA. This study used circular dichroism of supercoiled DNA and showed that Al- D-Asp caused a native B-DNA to C-DNA conformational change, while Al- L-Asp, Al- L-Glu and Al- D-Glu did not alter the native B-DNA conformation. This differential DNA binding property of Al-amino acid complexes is assigned to the stereoisomerism and chirality of the complexes. Interestingly, polyamines like spermine further induced an asymmetric condensation of the "limit C-motif" induced by Al- D-Asp to a Psi-DNA. The results were supported by computer modeling, gel studies and ethidium bromide binding. We also propose a mechanism of Al- D-Asp binding and its ability to modulate DNA topology.