New High-Affinity Peptide Ligands for Kv1.2 Channel: Selective Blockers and Fluorescent Probes

Ignatova, A.A.; Kryukova, E.V.; Novoseletsky, V.N.; Kazakov, O.V.; Orlov, N.A.; Korabeynikova, V.N.; Larina, M.V.; Fradkov, A.F.; Yakimov, S.A.; Kirpichnikov, M.P.; Feofanov, A.V.; Nekrasova, O.V.

Авторы: Ignatova Anastasia A., Kryukova Elena V., Novoseletsky Valery N., Kazakov Oleg V., Orlov Nikita A., Korabeynikova Varvara N., Larina Maria V., Fradkov Arkady F., Yakimov Sergey A., Kirpichnikov Mikhail P., Feofanov Alexey V., Nekrasova Oksana V.
Журнал: Cells
Том: 13
Номер: 24
Год издания: 2024
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Номер статьи: 2096
DOI: 10.3390/cells13242096
Аннотация: Advanced molecular probes are required to study the functional activity of the Kv1.2potassium channel in normal and pathological conditions. To address this, a fully active Kv1.2channel fused with fluorescent protein mKate2 (K-Kv1.2) was engineered that has high plasmamembrane presentation due to the S371T substitution, and hongotoxin 1 (HgTx1) fused with eGFPat the C-terminus (HgTx-G) was produced. HgTx-G and HgTx1 N-terminally labeled with Atto488fluorophore were shown to be fluorescent probes of Kv1.2 in cells with dissociation constants (Kd)of 120 and 80 pM, respectively. K-Kv1.2 and HgTx-G were used as components of an analyticalsystem to study peptide blockers of the channel and helped to find out that Ce1 and Ce4 peptidesfrom Centruroides elegans venom possess high affinity (Kd of 10 and 30 pM) and selectivity for Kv1.2.Using molecular docking and molecular modeling techniques, the complexes of Kv1.2 with HgTx1,Ce1, and Ce4 were modeled, and determinants of the high affinity binding were proposed. Newfluorescent probes and selective blockers of Kv1.2 can be used to resolve Kv1.2-related challenges inneuroscience and neuropharmacology.
Добавил в систему: Орлов Никита Александрович

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New High-Affinity Peptide Ligands for Kv1.2 Channel: Selective Blockers and Fluorescent Probesстатья

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