Michael HANNON

Michael HANNON

Birmingham University, UK

Combining Nanoscience with Metallo-Supramolecular Recognition of DNA and RNA to Achieve Bio-Activity

Abstract:

We have developed a new class of metallo-supramolecular agents that bind strongly and preferentially to DNA and RNA Y-shaped junctions (3-way junctions; forks; bulges) in vitro and prevent DNA transactions [1]. They are taken up readily into cells and rapidly localise in cell nuclei, where the fork-binding agents interfere with the processing of DNA leading to cell cycle arrest followed by apoptosis, without inducing genotoxicity or mutagenicity [2].

Excitingly some agents show potent anti-viral activities through recognition of a specific RNA bulge motif in the HIV genome, and have agents with high anti-viral activity at concentration levels where the compounds are not cytotoxic to mammalian cells [3].

Beyond the genome, DNA can also be used to create interesting synthetic nanostructures. We now show that our cylinders can bind to these nanostructures, and the cylinders can modulate the nanostucture’s shape. The cellular uptake and activity of these nanostructure-cylinder composites will be described [4].

REFERENCES

[1] S. Phongtongpasuk, S. Paulus, J. Schnabl, R. K.. O. Sigel, B. Spingler, M. J. Hannon, E. Freisinger, Angew. Chem. Intl Ed, 52, (2013).11513-6; D.R. Boer, J.M.C.A. Kerckhoffs, Y. Parajo, M. Pascu, I. Uson, P. Lincoln, M.J. Hannon, M. Coll , Angew. Chem. Intl. Ed., 49, (2010) 2336-2339 ; [2] C. Ducani, A. Leczkowska, N.J. Hodges, M.J. Hannon, Angew. Chem. Intl. Ed., 2010, 49, 8942-8945 (2010)
[2] A.C.G. Hotze, N.J. Hodges, R.E. Hayden, C. Sanchez-Cano, C. Paines, N. Male, M.-K. Tse, C.M. Bunce, J.K. Chipman, and M.J. Hannon, Chemistry & Biology, 15, (2008), 1258-1267.
[3] L. Cardo, I. Nawroth, P.J. Cail, J.A. McKeating and M. J. Hannon, Scientific Reports, vol. 8, (2018) 13342.
[4] P.J. Cail, A. Mucha, S. Phontongpasuk, L. Wang, F. Shao, M.J. Hannon, unpublished

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