In recent years, small organic molecules have attracted a great deal of interests of scientists in new drug design targeting biological macro-molecules, such as proteins, enzymes, receptors and nucleic acids (DNA and RNA). The interactions of drug with DNA comprise noncovalent binding and covalent bonding. The former one is reversible but the later one is irreversible. Most of the interactions between drugs and DNA belong to reversible binding, except for aristolochic acids in some toxic herbs from Aristolochiaceae which damage DNA irreversibly.

Prof. Jiang’s studies revealed that some anti-cancer alkaloids, such as berberine and its synthesized dimer, chelerythrine, sanguinarine and nitidine can specifically interact with DNA through an intercalating mode. In order to clarify their molecular mechanism of anti-cancer activities, Prof. Jiang employed a combination of spectrometric and biomedical techniques, including mass spectrometry, fluorometric analysis, spectrophotomeric titration, ethidium displacement, DNA polymerase stop assay etc., to intensively investigate the noncovalent irreversible binding of these alkaloids to several types of DNA, such as double-stranded, bulged and G-quadruplex DNA. The studies covered, for example, measurement of binding constants to designed DNA with different sequences and discussion of structure-activity relationship of these alkaloids. In addition, a series of dimeric berberines were synthesized, which were found to be much stronger DNA-binding
agents.  

"Our data provided concrete evidence for the most reasonable arrangement of "Beads-on-a-String" structure of human telomeric DNA. Furthermore, a novel model for the binding of sanguinarine to "Beads-on-a-String" human telomeric DNA was established for the first time. This novel binding model supplied important guidance for structure-based anti-cancer drug design targeting human telomeric DNA, "Professor Jiang addressed particularly the results from the studies on the interaction between sanguinarine and G-quadruplex DNA which exists in telomere of human chromosome. "The alkaloid berberine is the main component of some common Chinese herbs, such as Rhizoma Coptidis ("Huang- Lian") and Cortex Phellodendri ("Huang-Bai"), whereas, sanguinarine and nitidine are being used as anti-microbial and anti-inflammatory agents in toothpaste and mouthwashes. The strong DNA-binding activities of berberine, sanguinarine and nitidine alert us to the safety concern of daily-used hygiene products containing these herbal alkaloids," Prof. Jiang commented from another angle on the significance of their DNA-binding research.