کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1357182 | 981209 | 2005 | 14 صفحه PDF | دانلود رایگان |
A library of polyamine–peptide conjugates based around some previously identified inhibitors of trypanothione reductase was synthesised by parallel solid-phase chemistry and screened. Kinetic analysis of library members established that subtle structural changes altered their mechanism of action, switching between competitive and non-competitive inhibition. The mode of action of the non-competitive inhibitors was investigated in detail by a variety of techniques including enzyme kinetic analysis (looking at both NADPH and trypanothione disulfide substrates), gel filtration chromatography and analytical ultracentrifugation, leading to the identification of an allosteric mode of inhibition.
A library of polyamine–peptide conjugates was synthesised and screened against the parasitic enzyme trypanothione reductase. Kinetic analysis revealed that subtle structural changes caused a switch from non-competitive to competitive behaviour. Further mechanistic studies of the non-competitive inhibitors led to the elucidation of an allosteric mechanism of action.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 13, Issue 14, 15 July 2005, Pages 4513–4526