Natasha McStay

Background: BSc. (Hons) Chemical and Pharmaceutical Chemistry – Dublin City University (2014).

Research Project: The properties of opioid scaffolds and non-viral compounds for modulating nucleic acid equilibrium binding affinity  and nucleic acid condensation for cancer therapeutic applications.

This project aims to develop novel opioids with potent nucleic acid binding activity that selectively target cancer cells overproducing the opioid receptors, and inhibit their proliferation by arresting cellular DNA synthesis. Using quantitative structural activity relationships (QSAR), the structural basis and therapeutic application of the novel opioid scaffolds will be investigated. Since it is already established that many cancer cells overproduce the opioid receptor, our goal is to exploit this phenotype by rationally designing opioid receptor activating molecules with potent DNA condensation properties. We have recently shown that tripodal opioid scaffolds can condense double stranded DNA at low drug loading.

The development of effective and safe carrier vectors capable of compacting and protecting DNA for gene therapy has become one of the greatest challenges for chemists and biologists. Advances have recently been made in the design and syntheses of non-viral gene vectors which is of high interest in the pharmaceutical industry. Following from the success of the opioid scaffolds condensation properties, we hope to develop a series of DNA condensing agents that are more accessible than the opioid scaffold by exploiting a "click chemistry" reaction to generate large libraries for fast and efficient screening purposes.

Funding body: Dublin City University School of Chemical Sciences

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