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The grand-polymer, DNA, has been produced an
immense refinement of ideas about a plethora of its structural
diversity beyond the first most reported double helical structure
half-century back. The Watson-Crick B-form double helix, one of a
large number of stable structures that DNA can form, however, seem
to be functionally limited. In contrast, non-B DNA structures with
different helical sense, different number of strands, and
alternative base interactions have been discovered (such as curved,
cruciformed, triplex, quadruplex; approximately one new DNA form
every 2 years in the past 4 decades) and known to relate to various
aspects of biological functions. In addition, DNA is currently being
recognized as a ‘generic’ material, instead of its
‘genetic’ nature, for material sciences. DNA-based self-assembly
is of the big buzzword which can be utilized for bottom-up system
based fabrication of unique bio-nano-constructs for structural DNA
nanotechnology. We are particularly interested in DNA sequences of
guanine (G)-rich tracts which are specially high-lighted due to
their potential to form G-quadruplex DNA structure. In addition to
their intense biological role in vivo, their tendency for
self-aggregation towards higher-ordered supramolecular structures
making them distinct for autonomously construction of bio-nano-architectures.
However, a directed search of quartet-based molecular building
blocks and the associated principle is vital in the programmed
assembly of entirely novel biomaterials. Recently, we reported a
single-base substitution effect on self-assembling nature of G-rich
dodecanucleotides shown by gel-electrophoresis, circular dichorism,
and molecular dynamics (GENE,
2005). A group of novel d(G4N3G4N)-type
sequences, where N is G or non-G base, were found to generate
ultra-stable supramolecular aggregates bearable against the
denaturants and nucleases and was further confirmed by atomic
force-microscopy (AFM). The extremely interesting images which are
showing the assembly in 3-D plane with the average heights of
aggregates four times or more of the measured height of
double-stranded B-DNA, making these candidates very distinct from
the aggregation products of other reported G-rich sequences.
Based on the facts thus revealed, we constructed a model, ‘G-lego’,
for the self-assembling phenomenon into 3-D plane: successively
kissing of a unitary G-quartet block through a switching of
intramolecular pairing.
In
this research, the final structural determinants are working out
using NMR analysis which will no doubt tune the proposed model and
their versatility to breakthroughs in nanobiotechnology and to open
the door for DNA-based applications in nanobiotechnology. We are
also investigating the critical effects of specific cations /
polyamines (Electrophoresis,
2003) to regulate G-quartet structures and
thus the associated functions.
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