Department of Chemistry, University of Oxford, Oxford, OX1 3TA, UK.
Structural Genomics Consortium, University of Oxford, Headington, OX3 7DQ, UK.
Chemistry. 2019 Feb 6;25(8):2019-2024. doi: 10.1002/chem.201804790. Epub 2019 Jan 8.
Human prolyl hydroxylases are involved in the modification of transcription factors, procollagen, and ribosomal proteins, and are current medicinal chemistry targets. To date, there are few reports on inhibitors selective for the different types of prolyl hydroxylases. We report a structurally informed template-based strategy for the development of inhibitors selective for the human ribosomal prolyl hydroxylase OGFOD1. These inhibitors did not target the other human oxygenases tested, including the structurally similar hypoxia-inducible transcription factor prolyl hydroxylase, PHD2.
人类脯氨酰羟化酶参与转录因子、原胶原蛋白和核糖体蛋白的修饰，是当前药物化学的靶点。迄今为止，关于不同类型脯氨酰羟化酶选择性抑制剂的报道较少。我们报告了一种基于结构信息的模板策略，用于开发选择性针对人类核糖体脯氨酰羟化酶 OGFOD1 的抑制剂。这些抑制剂不针对其他测试的人类加氧酶，包括结构相似的缺氧诱导转录因子脯氨酰羟化酶 PHD2。
