Professor Paul M. Cullis

Professor of Organic and Biological Chemistry

Head of Section and AccessAbility Tutor

Tel : +44 (0)116 252 2130

Email: pmc@le.ac.uk

Personal details

Publications

  1. Huang WC, Cullis PM, Raven EL, Roberts GC. Control of the stereoselectivity of styrene epoxidation by cytochrome P450 BM3 using structure-based mutagenesis.Metallomics. (2011) 3(4):410 – 416.
  2. Heyes, D. J.; Quinn, A; Cullis, P. M.; Lee, M.; Munro, A. W.; Scrutton, N. S.  Internal electron transfer in multi-site redox enzymes is accessed by laser excitation of thiouredopyrene-3,6,8-trisulfonate (TUPS). Chemical Communications (2009),   (9),  1124-1126.
  3. Hothi, P.; Lee, M.; Cullis, P. M.; Leys, D.; Scrutton, N. S. Catalysis by the Isolated Tryptophan Tryptophylquinone-Containing Subunit of Aromatic Amine Dehydrogenase Is Distinct from Native Enzyme and Synthetic Model Compounds and Allows Further Probing of TTQ Mechanism. Biochemistry (2008),  47(1),  183-194.
  4. Cullis, P. M., Green, R. E., Merson-Davies, L., Travis, N., Probing the mechanism of transport and compartmentalisation of polyamines in mammalian cells Chemistry & Biology (1999), 6, 717–729.
  5. Su, W., Gray, S. J., Dondi, R., G, Highly efficient synthesis of DNA-binding hairpin polyamides via the use of a new triphosgene coupling strategy Organic Letters (2009),  11(17), 3910-3913

      Research

      Our research interests are in the field of chemical biology and are focused on investigating problems at the life sciences interface including:

      • fundamental studies on enzyme reaction mechanisms
      • development of new methods to control gene expression
      • development of molecular probes to unravel cell signalling in both the malaria parasite and mammalian cells

      Additional information

      The areas of research below are aimed at understanding important chemical and biological pathways and developing new diagnostic and therapeutic agents. They provide experience in synthetic chemistry, spectroscopic methods, especially high field multinuclear NMR spectroscopy (1H, 19F, 13C, 31P), mass spectrometry, infrared, GC, HPLC and X-ray crystallography.

      Research interests

      You can also find current postgraduate opportunities online.

      Design and synthesis of molecular probes

      PMC 1
      Design of molecular probes for protein kinases: deconvolution of the mammalian and malaria kinome

      The group is involved in the design and synthesis of molecular probes to unravel important biological processes and identify potential therapeutic targets. Current specific projects include development of probes to deconvolute protein phosphorylation in both mammalian cells and the malaria parasite (with Dr Glenn Burley and Prof Tobin), and synthesis of probes to investigate the structure and function of P2X receptors (with Prof Evans).

          Drug delivery and targeting

          Chemical approaches to disease try to address strategies for diagnosis and therapeutic intervention.

          PMC 2
          Design of novel modular theranostic devices: the polyamine achieves intracellular delivery, the fluorescent core provides detection (diagnosis) and the reporter group is the site for ultimate attachment of the therapeutic agent. Click to enlarge picture.

          Studies within the group on polyamine uptake in cells suggest that this may be exploited in terms of both diagnosis (of cancer) and delivery of chemotherapeutic agents (with Dr Lowe). We have designed a range of multifunctional molecular vectors incorporating delivery, diagnostic and therapeutic moieties (theranostics).

          Publication

          1. Cullis, P. M., Green, R. E., Merson-Davies, L., Travis, N., Probing the mechanism of transport and compartmentalisation of polyamines in mammalian cells Chemistry & Biology (1999), 6, 717–729.

            Development of polyamides as tools and therapeutic agents

            Strategies for selective gene knock-down such as RNAi provide powerful tools for molecular biologists. We have been developing a small molecule alternative that exploits the sequence-specific binding of polyamides derived from imidazole and pyrrole amino acids to the minor groove of DNA (with Dr Glenn Burley).

            Polyamides such as this can be used as tools and as therapeutic targets. Current projects are looking at their use in cardiovascular disease and in cancer chemotherapy.

            Publication

            Su, W., Gray, S. J., Dondi, R., G, Highly efficient synthesis of DNA-binding hairpin polyamides via the use of a new triphosgene coupling strategy Organic Letters (2009),  11(17), 3910-3913

            PMC 4
            Polyamide gene knockdown strategies: (C) Fluorescently labelled polyamide (FITC) showing localisation in the nucleus of hepatocytes. Polyamides can disrupt transcription factor binding and selectively turn off gene expre ssion.

            PMC 3
            Polyamide gene knockdown strategies: (A) Hairpin polyamide; (B) Polyamides bind sequence specifically to the minor groove of DNA. Click to enlarge picture.

             

             

             

             

             

             

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                Contact Details

                Department of Chemistry
                University of Leicester
                Leicester, LE1 7RH, UK

                Email: chemistry@le.ac.uk

                Tel: [+44] (0)116 252 2100

                Fax: [+44] (0)116 252 3789

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