Dixon Mark J, Maurer Richard I, Biggi Cristina, Oyarzabal Julen, Essex Jonathan W, Bradley Mark
School of Chemistry, University of Southampton, Southampton SO17 1BJ, UK.
Bioorg Med Chem. 2005 Jul 15;13(14):4513-26. doi: 10.1016/j.bmc.2005.04.039.
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.
围绕一些先前鉴定出的锥虫硫醇还原酶抑制剂，通过平行固相化学合成并筛选了一个多胺 - 肽缀合物文库。对文库成员的动力学分析表明，细微的结构变化改变了它们的作用机制，在竞争性抑制和非竞争性抑制之间切换。通过多种技术，包括酶动力学分析（观察NADPH和锥虫硫醇二硫化物底物）、凝胶过滤色谱法和分析超速离心法，详细研究了非竞争性抑制剂的作用模式，从而确定了变构抑制模式。
