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

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 Y-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.