Twyman, Lance J. - University of Sheffield

个人简介

Dr. Twyman obtained a BSc in Chemistry from King's College London in 1991, which was followed by a PhD from the University of Kent in 1995. After his PhD he became a postdoctoral research associate at the University of Cambridge and a Research Associate at Girton College. In 1997 he became a postdoctoral research fellow at the University of Oxford. In 1998 he was appointed as a lecturer at Lancaster University. In 2000 he was appointed as lecturer at the University of Sheffield, where he was promoted to senior lecturer in 2008.

研究领域

Drug delivery The therapeutic effectiveness of any drug is often diminished by its inability to gain access to the site of action in an appropriate dose. This is often due to the poor solubility of the drug in the body’s aqueous environment. One method of aiding solubilisation is to encapsulate the drug within the hydrophobic domains of a globular polymer. In our group we are investigating the use of dendrimers (shown in Figure 1 below), hyperbranched polymers and other polymeric systems, as encapsulation and delivery agents. Figure_1_LJTFigure 1: A water-soluble dendrimers that can be used to solubilize and deliver hydrophobic drugs. Supramolecular chemistry Supramolecular chemistry can be used to form discrete self assembled structures capable of performing a variety of functions. Our interest in this area has led to the development of supramolecular polymers that form a variety of structures. These include linear and dendritic polymers for use as potential light harvesting systems. We are also investigating the use of certain diblock polymers that can self assemble into spherical materials (single and bilayered) possessing microenvironments that can be exploited as catalysts for a variety of reactions. Figure_2_LJT Figure 2: Schematic of a supramolecular polymer capable of bind two reactive substrates leading to catalysis. Model enzymes and proteins - biomimetics Over millions of years Nature has evolved a series of molecules capable of performing a variety of important biological functions. These include catalysis, transportation and signalling. We are attempting to create much simpler synthetic analogues of these molecules. The principle aim is to engineer molecules capable of outperforming the natural systems they aspire to imitate. One example could include a catalyst that works for ALL oxidations, rather than one evolved to catalyse a single specific example. Alternatively, we could construct a catalyst that can generate non-natural isomers. As well as catalysis, related systems could be developed with important medical benefits. One such area includes our work on the development of artificial blood. Towards these aims we are exploiting a number of systems, which include self assembling polymers and globular dendritic molecules such as the oxygen binding system shown in Figure 3. Figure_3_LJT Figure 3: Porphyrin cored hyperbranched polymer that can reversibly bind oxygen, as well as catalyse as series of oxidation reactions. Protein binding Proteins bind and recognise each other using large surface areas. This recognition process is vital for a variety of biological applications. Understanding these interactions, as well as being able to inhibit them, may lead the development of new therapeutic molecules. Towards these aims we are exploiting the well-defined shape and size of certain globular macromolecules. Specifically we are using a series of dendrimers to study and inhibit protein-protein binding. Our initial results clearly indicate a simple size relationship between dendrimer and selective protein binding. That is, smaller dendrimers can interact preferentially with proteins possessing smaller binding areas, whilst larger dendrimers can interact preferentially with proteins possessing larger binding areas. Figure_4_LJT Figure 4: Screening results for dendrimer-protein binding.) The smaller G2.5 dendrimer is the strongest binder for cytochrome-c (smaller binding area), whilst the larger G3.5 dendrimer is the best inhibitor/binder for the protein chymotrypsin (larger binding area).

近期论文

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Dorniani D, Saifullah B, Barahuie F, Arulselvan P, Hussein MZ, Fakurazi S & Twyman LJ (2016) Graphene Oxide-Gallic Acid Nanodelivery System for Cancer Therapy.. Nanoscale Research Letters, 11(1), 491-491. View this article in WRRO Twyman LJ, Mann G & Ellis (2016) Modifying the product distribution of a reaction within the controlled microenvironment of a colloidosome. Macromolecules, 49(11), 4031-4037. View this article in WRRO Twyman LJ & Clixby G (2016) Self-Replicating Systems. Organic & Biomolecular Chemistry, 14, 4170-4184. View this article in WRRO Twyman LJ, Mann G & Gale PA (2016) Controlling microenvironments and modifying anion binding selectivities using core functionalised hyperbranched polymers. Chemical Communications (London), 52, 6131-6133. View this article in WRRO Twyman LJ & Zheng X (2016) A convenient synthesis of a porphyrin cross-linked polymer, its application as a size selective heterogeneous catalyst and a comparison with a porphyrin-cored hyperbranched polymer. Supramolecular Chemistry, 28(7-8), 617-623. Waris G, Siddiqi HM, Twyman LJ, Hussain R, Akhter Z & Butt MS (2013) Novel flame retardant poly(thiourea-sulfone-imide)s for high temperature applications: synthesis and characterization. TURKISH JOURNAL OF CHEMISTRY, 37(6), 946-958. Ellis A, Wallace M & Twyman LJ (2013) Exploiting dense shell/packing principles to invoke stereoselectivity in a reaction accelerated by a chiral dendrimer.. Chem Commun (Camb), 49(73), 8063-8065. View this article in WRRO