Advancements in Genetic Engineering
Open Access

OReilly RJ1

Biography

Robert J. O'Reilly is currently working as an Assistant Professor in Chemistry Department at Nazarbayev University. He has completed his Phd from 2007-2012 in Chemistry in School of Chemistry, The University of Sydney, supervised by Professor Leo Radom and the Thesis title: "Oxidative Damage to Biological Systems: A Theoretical Investigation". Followed by 2002-2006 BSc(Hons, 1) in Chemistry at School of Chemical and Physical Sciences, Victoria University of Wellington and Thesis title: "Towards a Polymer-Supported Synthesis of Isothiocyanates" 

Research Interest

Free-radical induced oxidative damage
Free radicals may damage biologically-important molecules, such as proteins, via hydrogen-atom abstraction reactions. Formation of carbon-centered radicals, particularly at the alpha positions of the individual amino acid residues, can culminate in protein degradation. On the other hand, electrophilic radicals (such as the ubiquitous OH•) appear to resist attack at the alpha position, with such reactions becoming generally more facile at sites further along the side chains. Modelling the factors that affect the regioselectivity of H-atom abstraction reactions from amino acids (and proteins) using quantum chemical calculations is therefore highly desirable.

The formation and decomposition of N-Chlorinated and N-Brominated Species
During the inflammatory response, activated white blood cells (neutrophils, eosinophils, lymphocytes etc...) secrete the enzyme myeloperoxidase (or eosinophil peroxidase in the case of eosinophils). These enzymes are responsible for catalyzing the oxidation of Cl– and Br– into the hypohalous acids HOCl and HOBr. The hypohalous acids are potent oxidants and react readily with the nitrogen-containing functional groups of proteins and DNA. The ensuing N-halogenated species, by virtue of the substantially weaker nature of N-Cl/N-Br vs N-H bonds, are better able to undergo bond cleavage reactions, affording damaging nitrogen-centered radicals. Radical formation allows for structural modifications, and such modifications may lead to genetic instability. As a result, it is desirable to understand the effect of structure on the stability of N-halogenated species. Special interest is given to the derivatives formed on the nucleobases of DNA/RNA, as well as amino acids (and proteins).

Prodrugs used for the delivery of anti-cancer agents
It is of interest to develop prodrugs that may be used to deliver two anticancer drugs simultaneously. The fragmentation reactions of 1,4,2-oxathiazole derivatives, which upon fragmentation afford both a carbonyl and an isothiocyanate, make such species potentially useful in this regard. Isothiocyanates have been well studied, and it is now widely established that they exhibit potent anticancer and anticarcinogenesis activity. Many chemotherapy drugs contain carbonyl moieties, and so may be incorporated into the heterocyclic system for later formation.  

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