Fernandes Andreia S, Morais-Cabral João H, Harley Carol A
IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
J Biomol Screen. 2016 Aug;21(7):758-65. doi: 10.1177/1087057116636592. Epub 2016 Mar 14.
Members of the ether-à-go-go (EAG) family of voltage-gated K(+) channels are involved in several pathophysiological diseases, and there has been a great interest in screening for drugs that modulate the activity of these channels. Many drugs have been shown to bind in the pore of these channels, blocking ion flux and causing disease pathology. In this report, we present two independent screening campaigns in which we wanted to identify small molecules that bind to either the intracellular cytoplasmic amino terminal Per-Arnt-Sim (PAS) domain from the human EAG-related gene (ERG) channel or the amino or carboxy terminal globular domains from the mouse EAG1 channel, affecting their interaction. We report that in both cases, compounds were identified that showed weak, nonspecific binding. We suggest alternative routes should be pursued in future efforts to identify specific, high-affinity binders to these cytoplasmic domains.
电压门控钾离子通道的醚 - 去 - 去（EAG）家族成员与多种病理生理疾病有关，因此人们对筛选调节这些通道活性的药物产生了浓厚兴趣。许多药物已被证明能结合在这些通道的孔中，阻断离子通量并导致疾病病理。在本报告中，我们展示了两项独立的筛选活动，我们希望识别与人类EAG相关基因（ERG）通道的细胞内胞质氨基末端Per-Arnt-Sim（PAS）结构域或小鼠EAG1通道的氨基或羧基末端球状结构域结合的小分子，从而影响它们的相互作用。我们报告称，在这两种情况下，都鉴定出了显示出弱的、非特异性结合的化合物。我们建议在未来识别这些胞质结构域的特异性、高亲和力结合剂的工作中应寻求其他途径。
