Dr Nicola Howarth
BSc, PhD, CChem, MRSC
- +44 (0)131 451 8026
William Perkin Building
Roles and responsibilities
- Fourth Year Study Director [BSc (Hons)]
- Programme Leader for ‘Chemistry with Biochemistry’ Degrees‘
- Staff Student Liaison Committee’ Representative
Our principal research interests lie in the development of novel therapeutic agents for potential use in the treatment of cancer, HIV-1 and bacterial infections. We also have interests in the development of novel nucleic acid biosensors and new in vitro methods for determining key pharmacological parameters of pharmaceutical drugs (e.g. log P, permeability, etc); the latter is undertaken in collaboration with Dr. Arno Kraft.
1. DNA-Binding Ligands
The ability to selectively modulate gene expression will make a major impact in the treatment of a variety of human diseases. Our approach centres on the development of ligands which will bind to DNA in a sequence-selective manner so as to inhibit transcription. The majority of our research in this area is focused on the design and synthesis of novel DNA analogues in which the original sugar-phosphate backbone has been replaced by a peptide backbone e.g. alpha-PNA, alpha-cycloPNA (Figure 1).
Figure 1. Comparison of the structures of DNA, alpha-PNA and alpha-cycloPNA.
2. Anti-HIV-1 Agents
Despite the success of HAART, AIDS remains one of the most urgent world health problems. The therapeutic situation is challenged by rapid emergence of drug resistant strains and so new anti-HIV drugs are needed. We have identified a novel family of non-nucleoside reverse transcriptase inhibitors exemplified by N2-benzyloxycarbonylguan-9-yl acetic acid derivatives 1 (Figure 2). These derivatives were found to be less sensitive to common drug-resistant mutant strains than known NNRTIs.
Figure 2. Structure of N2-benzyloxycarbonylguan-9-yl acetic acid derivatives.
3. Nucleic Acid Biosensors
The ability to identify particular nucleic acid sequences, both quickly and precisely, has become of increasing importance in recent years. We have embarked on a project to develop a novel colourimetric biosensor in which peptide nucleic acid (PNA)-functionalised lipids are incorporated into polydiacetylene (PDA) liposomes; the PNA is the detector and PDA the sensor. It is envisaged that when PNA binds to its target gene, PDA will be induced to change colour from blue to red (Figure 3).
Figure 3. Blue liposome solutions prepared from 100% matrix lipid 10,12-PCDA (far left) and two component mixtures of PNA-functionalised lipids (5%) with 10,12-PCDA (95%).
Ongaro, A. E., Keraite, I., Liga, A., Conoscenti, G., Coles, S., Schulze, H., ... Kersaudy-Kerhoas, M. (2018). Laser Ablation of Poly(lactic acid) Sheets for the Rapid Prototyping of Sustainable, Single-Use, Disposable Medical Microcomponents. ACS Sustainable Chemistry and Engineering, 6(4), 4899–4908. DOI: 10.1021/acssuschemeng.7b04348. Link
Gakamsky, A., Duncan, R. R., Howarth, N. M., Dhillon, B., Buttenschön, K. K., Daly, D. J., & Gakamsky, D. (2017). Tryptophan and Non-Tryptophan Fluorescence of the Eye Lens Proteins Provides Diagnostics of Cataract at the Molecular Level. Scientific Reports, 7, . DOI: 10.1038/srep40375. Link
Kitson, M., Sheppard, H. N., Morris, J. C., Howarth, N. M., & Kraft, A. M. (2014). A Low-Cost Method for Measuring the Permeability of a Pharmaceutical Drug in a Diffusion Cell. Chemical Educator, 19, 310-313. DOI: 10.1333/s00897142584a. Link
Heuer-Jungemann, A., Howarth, N. M., Ja’afaru, S. C., & Rosair, G. M. (2013). Development of a convenient route for the preparation of the N 2-Cbz-protected guaninyl synthon required for Boc-mediated PNA synthesis. Tetrahedron Letters, 54(46), 6275-6278. DOI: 10.1016/j.tetlet.2013.09.034 Link
Howarth, N. M., & Goujon (nee Ricci), J. (2011). Synthesis of N-propynyl analogues of peptide nucleic acid (PNA) monomers and their use in the click reaction to prepare N-functionalized PNAs. Tetrahedron, 67(49), 9588-9594. DOI: 10.1016/j.tet.2011.09.124. Link
Up-to-date publications are listed on this research profile.