Key result
Mutation of Kv1.1 turret residues to match the sequence of Kv1.3 led to increased inhibition of Kv1.1 activity by the ADWX-1 peptide inhibitor.
The Kv1 turret is the critical determinant for ADWX-1 peptide inhibitor selectivity of Kv1.3 over Kv1.1, which may guide future peptide inhibitor drug development.
May guide selective Kv1.3 inhibitor design; leaves open clinical translation of turret modifications.
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.
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Yin et al. (2008) studied this question. ADWX-1 peptide inhibitor was evaluated on Inhibition of Kv1.1 activity. Mutation of Kv1.1 turret residues to match the sequence of Kv1.3 led to increased inhibition of Kv1.1 activity by the ADWX-1 peptide inhibitor.
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