Highlight publications
Publications currently and previously highlighted on the WSP homepage
J.H. Vernachio, B. Bleiman, K.D. Bryant, S. Chamberlain, D. Hunley, J. Hutchins, B. Ames, E. Gorovits, B. Ganguly, A. Hall, A. Kolykhalov, Y. Liu, J. Muhammad, N. Raja, R.C. Walters, J. Wang, K. Williams, J.M. Patti, G. Henson, K. Madela, M. Aljarah, A. Gilles, C. McGuigan
Antimicrob Agents, Chemother, 2011, 1843-1851. doi:10.1128/AAC.01335-10
In this paper the collaborative Cardiff-Inhibitex team describe in detail the biological and therapeutic profile of their lead anti-HCV agent INX-08189. Data are generated in vitro and in vivo that demonstrate the major potential of this agent, which has recently entered human clinical trial vs hepatitis C.
Martin CJ, Allender CR , Brain KR, Morrissey A and Birchall JC .
Journal of Controlled Release DOI:10.1016/j.jconrel.2011.10.024 (2011).
This paper describes a completely novel process and material for preparing biodegradable microneedles. Sugar glass microneedles are simple to prepare, robust and drug-loadable and demonstrate particular promise for minimally-invasive delivery of biologics.
Christopher McGuigan , Paola Murziani, Magdalena Slusarczyk, Blanka Gonczy, Johan Vande Voorde, Sandra Liekens, and Jan Balzarini
J. Med. Chem. 2011, 54, 7247–7258.
Gomaa, M. S.; Bridgens, C. E.; Aboraia, A. S.; Veal, G. J.; Redfern, C. P.; Brancale, A. ; Armstrong, J. L.; Simons, C ., J Med Chem 2011, 54 (8), 2778-91.
This manuscript describes the development and SAR of potent inhibitors of CYP26A1 with potential in the treatment of hyperproliferative disease, culminating in a lead inhibitor with low nM activity, good CYP selectivity, good stability (t1/2 5h human liver microsomes) indicating negligible phase I metabolism and no mutagenic potential.
Immunoprotection against toxic biomarkers is retained during Parkinson's disease progression.
Gruden, M. A., Sewell R. D. E. , Yanamandra, K., Davidova, T. V. Kucheryanu, V. G., Bocharov E. V., Bocharova O. R., Polyschuk, V.V., Sherstnev V.V.,. Morozova-Roche L. A.
Neuroimmunol (2011) 233, 221-227. doi:10.1016/j.jneuroim.2010.12.001
The work has demonstrated a link between patient immune responses to the Parkinson’s disease associated protein alpha synuclein in the toxic oligomer and fibril stages which can aggregate in pathological conditions characterised by Lewy bodies. Early detection of antibodies to these oligomer and fibrillar stages has the potential for diagnosis of the disease
This is the latest output of a collaboration of Dr Sewell with both the Russian and Swedish groups for nearly ten years.
J.H. Vernachio, B. Bleiman, K.D. Bryant, S. Chamberlain, D. Hunley, J. Hutchins, B. Ames, E. Gorovits, B. Ganguly, A. Hall, A. Kolykhalov, Y. Liu, J. Muhammad, N. Raja, R.C. Walters, J. Wang, K. Williams, J.M. Patti, G. Henson, K. Madela, M. Aljarah, A. Gilles, C. McGuigan
Antimicrob Agents, Chemother, 2011, 1843-1851. doi:10.1128/AAC.01335-10
In this paper the collaborative Cardiff-Inhibitex team describe in detail the biological and therapeutic profile of their lead anti-HCV agent INX-08189. Data are generated in vitro and in vivo that demonstrate the major potential of this agent, which has recently entered human clinical trial vs hepatitis C.
The McGuigan group in Cardiff did all of the medicinal chemistry in this paper. We designed and made the compound, plus all backups. We contributed to the paper in draft and at correction stage. We are co-authors with Inhibitex with a senior (anchor) spot on the paper, in high impact journal Antimicrob Ag Chemother.
Vercauteren, D., Piest, M., van der Aa, L.J., Al Soraj, M., Jones, A.T., Engbersen, J.F.J., De Smedt, S.C and Braeckmans, K.
Biomaterials, (2011) doi:10.1016/j.biomaterials.2010.12.045
This paper describes, for the first time, how siRNA depletion of multiple endocytic proteins and pathways can be used to study the cellular uptake and tansfection capacity of polyplexes that are of interest as potential drug delivery vectors.
Within this tripartite international collaboration, the School of Pharmacy's focus was on identifying optimal siRNA sequences and depletion conditions, as well as characterising methods for analysing protein expression in siRNA treated cells.
Anti-amyloid-β protein precursor antibodies inhibit amyloid-β production by steric hindrance.
Thomas, R.S., Liddell, J.E. and Kidd, E.J. (2011).
FEBS Journal, 278, 167-178, DOI 10.1111/j.1742-4658.2010.07942.x
This paper proves the mechanism of action of our novel, potential therapeutic antibodies against amyloid precursor protein and highlights the excellent activity of one of the antibodies, 2B3, which is the subject of a patent application.
Les W. Baillie, Theresa B. Huwar, Stephen Moore, Gabriela Mellado-Sanchez, Liliana Rodriguez, Brendan N. Neesond, Helen C. Flick-Smith, Dominic C. Jenner, Helen S. Atkins, Rebecca J. Ingram, Danny M. Altmann, James P. Nataro, Marcela F. Pasetti
VaccineVolume 28, Issue 41, 24 September 2010, Pages 6740-6748
This manuscript describes the results of a multi-national study in which we characterised the murine and human immune response to the two components that make up Lethal Toxin, the major virulence factor produced by Bacillus anthracis the causative agent of anthrax. The current human anthrax vaccine is produced so as to maximise the content of Protective Antigen (PA), the non toxic cell binding element of Lethal toxin. Concerns over the ability to genetically engineer strains of B.anthracis so that they produce a variant of PA which is no longer recognised by the vaccine has prompted researchers to investigate alternative vaccine candidates. We adopted an immunological approach in which we identified and incorporated the key protective region of PA and Lethal Factor (LF) the second enzymically active constituent of Lethal toxin, into a single fusion protein. Such a protein would broaden the spectrum of protection making if more difficult to subvert by genetic engineering and would greatly simply the manufacturing process. Using this approach we constructed a single fusion protein which stimulated robust immune responses and protected mice against a lethal anthrax spore challenge.
In vitro reporter gene transfection via plasmid DNA delivered by metered dose inhaler.
Bains, B.K., Birchall, J.C. , Toon, R. and Taylor, G .
J. Pharm. Sci. 99: 3089-3099 (2010).
This paper is the first report of the successful incorporation and aerosolisation of DNA material in a pressurised metered dose inhaler. Whilst the results show proof of principle the potential applications for gene delivery (and perhaps viral components) to the lung are wide-ranging.
Pearton M , Kang SM, Song JM, Anstey AV, Ivory M, Compans RW and Birchall JC .
PLoS One (2010) e12410.
The first paper to describe how influenza vaccines initiate local immune response in live human skin.
F.M. Hajjaj, M.S. Salek , M.K.A. Basra and A.Y. Finlay
British Journal of Dermatology, 2010 (Early View)
C. McGuigan, A. Gilles, K. Madela, M. Aljarah, et al.
J. Med. Chem., 2010, 4949-4957.
This describes our drug discovery programme with Inhibitex on HCV, from hit to lead, and leading onto the clinical candidate 189, just in phase 1.
Chew E-H, Nagle AA, Zhang Y, Scarmagnani S, Palaniappan P, Bradshaw TD, Holmgren A, Westwell AD
Free Rad. Biol. Med. (2010), 48, 98-111.
The discovery of natural product-derived antitumour cinnamaldehydes with either chemopreventative or chemotherapeutic properties dependent on dose.
Rebecca J. Ingram, Gökhan Metan, Bernard Maillere, Mehmet Doganay, Yusuf Ozkul, Louise U. Kim, Les Baillie , Hugh Dyson, E. Diane Williamson, Karen K. Chu, Stephanie Ascough, Steven Moore, Theresa B. Huwar, John H. Robinson, Shiranee Sriskandan, and Daniel M. Altmann
J Immunol. published online March 5, 2010, doi:10.4049/jimmunol.0901581
...
Henney N, Li B, Elford C, Reviriego P, Campbell A, Wann K , Evans B.
Am J Physiol Cell Physiol (2009)
The 1st paper to describe the pharmacological profile of a subtype of K channel (BK channel) in osteobasts (bone cells) and to implicate one subtype of the BK channel in cell growth and the mineralisation process.
Watkins C, Schmaljohann, D., Futaki, S., and Jones, A.T.
Biochem J. (2009) 420 (2) 179-189
This highlights the high porosity of plasma membranes to cationic cell penetrating peptides, thus opening new avenues for their use as vectors for bio-active entities.
Morgan L, Gee J, Pumford S, Farrow L, Finlay P, Robertson J, Ellis I, Kawakatsu H, Nicholson RI and Hiscox S
Cancer Biology and Therapy (2009) 8(16):23-31
A translational study that supports our previous in vitro observations suggesting that Src kinase is an important determinant of the therapeutic response of breast cancers
ATP Regulates Calcium Efflux and Growth in E. coli
Riffat Naseem, Kenneth T. Wann, I. Barry Holland and Anthony K. Campbell
J. Mol. Biol. (2009), 391, 42-56.
Effects of dietary amines on the gut and its vasculature.
Broadley KJ, Akhtar Anwar M, Herbert AA, Fehler M, Jones EM, Davies WE, Kidd EJ, Ford WR.
Br J Nutr. (2009), Jun;101(11) :1645-52.
Hughes, M. Louise; John, Dai N.; Jones, Arwyn T. Jones, Elen H.; Wilkins, M. Lowri
International Journal of Pharmacy Practice, Volume 17, Number 3, June 2009 , pp. 157-163(7)
Clinical administration of microneedles:skin puncture, pain and sensation.
Haq, MI, Smith E, John DN, Edwards, C., Kalavala, M., Anstey, A., Morrissey, A, Birchall JC. Biomedical Microdevices (2009) 11:35-47. ISSN 1387-2176
A glimpse of the inner workings of the templated site.
Christopher J. Allender, Oliver K. Castell, Philip R. Davies, Steven Fiddy, Jimmy Hedin-Dahlström and Michael Stockenhuber
Chem. Commun., (2009), 165 - 167, DOI: 10.1039/b811578h
C McGuigan, M Serpi, R Bibbo, H Roberts, C Hughes, B Caterson, A Gibert, C Verson,
J. Med. Chem., (2008), 51, 5807-5812.
Gomaa, M.S.; Armstrong, J.L.; Bobillon, B.; Veal, G.J.; Brancale, A.; Redfern, C.P.F. and Simons, C.,
Bioorganic and Medicinal Chemistry, (2008), 16, 8301-8313.
Baillie LW, Rodriguez AL, Moore S, Atkins HS, Feng C, Nataro JP, Pasetti MF.
Vaccine (2008), 26(48) :6083-91.