DNA, having been studied by researchers for decades, remains one of the most promising therapeutic targets in many interaction processes. The most common example of this type of interaction is cisplatin with the guanine nucleobase. Cisplatin recognizes, binds and kinks the DNA, preventing further replication, making it a well-known cancer therapy. Non-canonical nucleobases that are part of DNA bulges, hairpin loops, mismatches or abasic sites are common targets when designing small molecules for binding both organic and inorganic compounds. For example, Zn(II) complexes containing planar aromatic pendents with two fused rings bind to DNA Hairpin (T-bulge/T-Loop) more tightly than complexes with non-planar pendents. A less common but still interesting DNA structure is the G quadruplex (loop). G-quadruplexes are four-stranded guanine-rich structures that are found in promoter regions of DNA or at the telomeric ends of DNA (they may be also play a role in m-RNA as well). A better understanding of these types of interactions as well as the development of alternative ways to recognize unusual nucleic acid structures, may lead to improved design of small molecules for future therapeutic applications. Toward this end, we report on the use of Reichert's surface plasmon resonance (SPR) system to characterize the binding of Zn complexes to DNA T-bulge and T-loop structures.
A summary of conditions used to study the binding of a Zn complex to two different types of DNA structures is provided here. In both cases, biotinylated DNA was injected over the sample channel only of a Streptavidin sensor chip. Biotinylation of DNA provides an easy and direct way to capture it onto the sensor chip surface. In addition, DNA biotinylated at only one point ensures that the DNA strand is in the desired orientation when captured onto the sensor chip surface. This study focuses on a Zn complex called Zn4Qone and the conditions used for this analysis are summarized in the following Table:
Sensorgrams and kinetic fits obtained for Zn4Qone binding to T-bulge DNA and T-loop DNA are shown in Figures 1 and 2, respectively. The Zn complex binds more tightly to the T-bulge than to the T-Loop target. This is a general trend seen when a series of Zn complexes were injected over these two types of DNA molecules. For more information on this topic, see the journal article Dalton Trans., 2015, Vol 44, pp. 3708–3716.
It has been demonstrated that Reichert SPR instruments offer outstanding ability to characterize DNA-small molecule interactions. Benefits of using Reichert SPR instruments for studying nucleic acid interactions include: