Recently, our group has made a series of progresses in the field of DNA catalysis. G-quadruplex DNAs (also known as G-tetrads or G4-DNA) are one of specific DNA sequences that are rich in guanine and are capable of forming a four-stranded structure. This structure takes on a close correlation with cancer. We have devoted to probing the biological function of DNA from the perspective of biocatalysis.
With Diels-Alder reaction as a probe, we have found that K+ and NH4+, bearing approximately equal ionic radius, present different allosteric activation for higher-order human telomeric G-quadruplex DNA metalloenzyme. The obtained major endo products of Diels-Alder reaction can be switched from one preferred configuration in K+ media to its mirror configuration in NH4+ media (Chem. Commun. 2015, DOI: 10.1039/C5CC05215G).
Especially, we found that a series of terpyridine–Cu(II) complexes (CuLn) can serve as excellent cofactors to dock with human telemetric G-quadruplex DNA. The resulting G-quadruplex DNA metalloenzyme utilising CuL1 catalyzes an enantioselective Diels–Alder reaction with enantioselectivity of >99% enantiomeric excess and about 73-fold rate acceleration compared to CuL1 alone (Chem. Sci. 2015, DOI: 10.1039/C5SC01381J). To the best of our knowledge, this is the most efficient G-quadruplex DNA metalloenzyme for Diels–Alder reaction reported so far. This finding might provide new insight into the mechanism of action of G-quadruplex-anticancer drug in cancer therapeutics from the perspective of biocatalysis.
This work is financially supported by National Natural Science Foundation of China. (By Guoqing Jia and Yinghao Li)
