Different Residues in Channel Turret Determining the Selectivity of ADWX-1 Inhibitor Peptide between Kv1.1 and Kv1.3 Channels
Different Residues in Channel Turret Determining the Selectivity of ADWX-1 Inhibitor Peptide between Kv1.1 and Kv1.3 Channels
复制标题
通道转塔中的不同残基决定了 ADWX-1 抑制肽在 Kv1.1 和 Kv1.3 通道之间的选择性。
DOI：
10.1021/pr800494a
复制
发表时间：
2008-11-01
影响因子：
4.4
通讯作者：
Li, Wen-Xin
中科院分区：
文献类型：
--
作者：
Yin, Shi-Jin;Jiang, Ling;Li, Wen-Xin
Kv 1肽抑制剂对特定亚型的低选择性使其成为开发治疗药物的不良候选物。使用组合方法，我们表明Kv 1转塔是ADWX-1肽抑制剂选择性Kv1.3超过Kv1.1的关键决定因素。突变Kv1.1转塔残基以匹配Kv1.3的序列导致Kv1.1活性的抑制增加。这些研究可能导致肽抑制剂药物开发的改进。
The low selectivity of Kv1 peptide inhibitors for specific isoforms makes them poor candidates for the development of theraputics. Using combined approaches, we showed that the Kv1 turret is the critical determinant for ADWX-1 peptide inhibitor selectivity of Kv1.3 over Kv1.1. Mutation of Kv1.1 turret residues to match the sequence of Kv1.3 lead to increased inhibition of Kv1.1 activity. These studies may lead to improvements in peptide inhibitor drug development.