Magdeline Tao Tao Ng

C3-Spacer-containing circular oligonucleotides as inhibitors of human topoisomerase I.

Some dumbbell-shaped circular oligonucleotides containing internal C3-spacers and Topo I-binding sites were designed and synthesized which displayed high inhibitory efficiency on the activity of human Topo I as well as resisted the degradation by some DNA repair enzymes.

Manipulating DNA writhe through varying DNA sequences.

It is demonstrated that the shapes and magnitudes of DNA writhe can be precisely manipulated solely through maneuvering the nucleotide sequence of DNA and without the assistance of topoisomerases.

Precise engineering and visualization of signs and magnitudes of DNA writhe on the basis of PNA invasion

It is demonstrated that the right and left handedness of DNA supercoils can be engineered precisely and readily at the molecular level in vitro through utilization of the invading property of peptide nucleic acid.

Nick-containing oligonucleotides as human topoisomerase I inhibitors

A series of oligonucleotides with various lengths that contain nick and topoisomerase I-binding sites were designed. The interactions between these oligonucleotides and human topoisomerase I were investigated and the most efficient one among them has displayed IC(50) value of 6.3 nM. Our studies have also demonstrated that the position of the nick as well as the length of the oligonucleotides were crucial factors for the inhibition of this nuclear enzyme.

Site specific self-cleavage of certain assemblies of G-quadruplex

It is demonstrated that certain structural assemblies of G-quadruplex are capable of performing selfcleaving actions in a site specific fashion.

Recognition of forcible curvature in circular DNA by human topoisomerase I

A series of forcible curved circular DNAs (cDNAs) were prepared to investigate the recognition features of human Topoisomerase I (hTopo I). The IC(50) can be modulated by the curvature degrees of cDNA. In addition, preferential bindings of hTopo I to cDNA with high curvature have been observed by AFM and EMSA.

Confirmation of quinolone-induced formation of gyrase–DNA conjugates using AFM

It was demonstrated in our studies that norfloxacin, a representative member of quinolone antibiotics, can indeed stabilize the gyrase-DNA complex formed during enzymatic cycle. In addition, the formation of the drug-induced complex has been firstly visualized through our atomic force microscopic examination.

Interference of intrinsic curvature of DNA by DNA-intercalating agents

It has been demonstrated in our studies that the intrinsic curvature of DNA can be easily interrupted by low concentrations of chloroquine and ethidium bromide. In addition, the changes of DNA curvature caused by varying the concentration of these two DNA intercalators can be readily verified through using an atomic force microscope.

Synthesis and Characterization of Circular Structures of i-Motif Tagged with Fluoresceins

Synthesis of a fluorescein-tagged circular structure of i-motif was accomplished during our investigations. The backbone circularity of this molecular probe and the presence of the fluorescent moiety within its structure were also confirmed through exonuclease hydrolysis and fluorescence spectroscopy.

Site-Specific Cleavage of G-quadruplexes Formed by Oxytricha Telometric Repeats

We demonstrate that certain G-quadruplex structures formed by Oxytricha telomeric repeats possess DNA-cleavage ability. Further studies verify that this cleavage activity is both site-specific and G-quadruplex-dependent.