d(GC) - Association of Biotechnology and Pharmacy

Current Trends in Biotechnology and Pharmacy
Vol. 6 (2) 204-209 April 2012, ISSN 0973-8916 (Print), 2230-7303 (Online)
For the comparative study interaction of Almaltol
with Poly (AT).d(AT) was also studied. As
the concentration of Al- maltol is increased there is
a decrease in the magnitude of both positive and
negative peaks at 260nm and 250nm respectively.
The 225nm positive peak of the Poly(AT).d(AT) has
been shifted to lower wavelength as the
concentration of Al-maltol is increased. But Al-maltol
did not cause any helical transition (Fig. 2).
Discussion
Poly d(GC). d(GC) undergoes Z-DNA
conformation from B-DNA by various factors like
high salt concentration (20), methylation of
deoxycytidine (21), high pressure ( 22), several
cations like Mg, Cd, Hg, Ni, and Co (23), binding of
peptides (24), polyamines like spermine (24) and
negative supercoiling in in vivo system (25). The
Z-DNA is first reported by optical studies
demonstrating that a polymer of alternating
deoxyguanosine and deoxycytidine residues
(d(CG) n ) produced a nearly inverted circular
dichroism spectrum in a high salt solution (20). The
Z-DNA helix is built from a dinucleotide repeat with
the deoxycytidines in the anti conformation and
deoxy guanosines are in the unusual syn
conformation (26, 27). Karlik (17) reported that
Aluminum stabilizes a portion of calf thymus DNA
at neutral pH and Al (OH) 2+ has been attributed for
the stabilization. At acidic pH Al destabilized the
DNA by intrastrand cross links. Studies on
interaction of Al with Poly d(GC). d(GC) showed
interstrand cross link at low pH (< 6) (17). The
primary binding of Al is the phosphate group and
through electrostatic interaction. There exists
controversy regarding its binding with nitrogen
bases. Ahmed et al (28 ) using FTIR spectroscopy
reported that Al cation bind mainly through the
backbone PO 2 group and guanine bases. The cross
linking of DNA strands by Al reported by Karlik et al
(17) also evidenced Al binding to bases since the
ability of metals to produce cross links appear to
result from affinity for the nucleotide bases. Al binds
weakly to basic phosphate group of DNA, while
basic and chelating phosphate groups of
206
nucleotides di and triphosphates do bind Al strongly.
Al- maltol is a water soluble (6x 10-2M) and
hydrophilic (28). Al- maltol don’t under go
hydrolysis chemistry from pH 2 to 12. Though
conductivity studies indicated that Al-maltol
remains uncharged in aqueous solutions, the
presence of charged species can not be ruled
out. According to Corain et al the speciation of
Al- maltol reveals that the thermodynamically
predicted species which dominate at pH 7.0 for
+ 2+ Al-maltol are Al (mal) and Al(mal)2 (29). In the
2
present study, under given experimental
conditions Al acts as monovalent and divalent
rather than the trivalent Al (Al3+ ) ion and movovalent
being predominant and moreover the Al-maltol
2+ + complex species, Al(mal) and Al(mal)2 bind to
2
DNA. It has been shown that Al (OH) 2+ do not
cross link the DNA strands (29). Binding of
+ 2+ Al(mal) and Al(mal) to the GC polynucleotide
2
might play role in the B-DNA to Z-DNA
conformational transition. There exists no definite
mechanism to explain the role of metals in
causing structural transitions. The possible ways
through which Al-maltol can cause structural
transition in GC polynuclelotide are given below.
Through phosphate binding, which alleviates
electrostatic repulsion thereby stabilizing base
pairing and base stacking. Al species could have
an influence on the water shell of DNA, which
would make the helix more flexible for
conformational change. It has been suggested
that reduction of DNA phosphate repulsion
(charge screening ) and polymer hydration state
are important determinants of conformation and
structural transitions (30) . Another mechanism
would be base-back binding of phosphate
coordinated metal ion to N-7 of guanosine there
by stabilizing the syn conformation of the guanosine.
The H(N1) sites of guanosine base are not available
for binding with metals at neutral pH and this leaves
N-3 and N-7 as targets. Among theses N-7 is the
most likely target for cation interaction while binding
to N-3 is exceptionally found (31-33). We propose
1+ 2+ that Al in its Al(mal) and Al(mal) forms stabilizes
2
syn conformation by base-back binding of the
First evidence for Aluminum-maltol driven B to Z-DNA