Pharmacology and Therapeutics - Research Publications

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    Synthesis of Peptide Sequences Derived from Fibril-Forming Proteins
    Scanlon, DB ; Karas, JA ; Hill, AF ; Barnham, KJ ; Bottomley, SP ; Cappai, R (HUMANA PRESS INC, 2011)
    The pathogenesis of a large number of diseases, including Alzheimer's Disease, Parkinson's Disease, and Creutzfeldt-Jakob Disease (CJD), is associated with protein aggregation and the formation of amyloid, fibrillar deposits. Peptide fragments of amyloid-forming proteins have been found to form fibrils in their own right and have become important tools for unlocking the mechanism of amyloid fibril formation and the pathogenesis of amyloid diseases. The synthesis and purification of peptide sequences derived from amyloid fibril-forming proteins can be extremely challenging. The synthesis may not proceed well, generating a very low quality crude product which can be difficult to purify. Even clean crude peptides can be difficult to purify, as they are often insoluble or form fibrils rapidly in solution. This chapter presents methods to recognise and to overcome the difficulties associated with the synthesis, and purification of fibril-forming peptides, illustrating the points with three synthetic examples.
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    Elucidating the Role of Metals in Alzheimer's Disease Through the Use of Surface-Enhanced Laser Desorption/Ionisation Time-of-Flight Mass Spectrometry
    Watt, AD ; Perez, KA ; Hung, LW ; Hill, AF ; Barnham, KJ ; Bottomley, SP ; Cappai, R (HUMANA PRESS INC, 2011)
    Alzheimer's disease (AD) is a highly heterogeneous and progressive dementia which is characterised by a progressive decline in cognitive functioning, selective neuronal atrophy, and loss of cortical volume in areas involved in learning and memory. However, recent research has indicated that the AD-affected brain is also besieged by increases in oxidative stress as well as perturbations to the homeostasis of biometals, such as copper and iron. These metals are known to interact with the neuropathological hallmark of AD, the β-amyloid peptide (Aβ), in a manner which increases Aβ's neurotoxic effects. This knowledge has led to the development of therapeutic measures which act to restore biometal homeostasis within the AD brain. This chapter outlines how Surface-Enhanced Laser Desorption/Ionisation Time-of-Flight Mass Spectrometry can be used to monitor Aβ levels within biological systems as well as describing the use of immobilised metal affinity capture in the observation of synthetic Aβ peptides.
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    Purinergic Receptors and Pain-An Update
    Burnstock, G ; AttaUrRahman, ; Choudhary, MI ; Reitz, AB (BENTHAM SCIENCE PUBL, 2016)
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    The composition and actions of Papua New Guinean snake venoms
    Williams, DJ ; WELTON, R ; Williams, DJ ; Jensen, SD ; Winkel, KD (Independent Publishing, 2004-05-01)
    Snake venoms are complex mixtures of bioactive agents with diverse pharmacological activities against a wide range of physiological targets. Many of these agents are complex chemicals which have toxic effects upon the cells and cellular mechanisms that they target, and in some snakes the toxicity is sufficient to be extremely harmful to man. Understanding the composition and activities of different snake venoms forearms clinicians with a knowledge of the underlying physiological changes responsible for clinical envenomation syndromes. In some cases this knowledge may enable presumptive identification of the biting species and early selection of the most appropriate antivenom.
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    Insect envenomation
    Winkel, KD ; Senthilkumaran, S (Wolters Kluwer, 2012)