Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses in vivo.
In vivo evidence is provided that Kv1.3 is a novel target for immunomodulation by demonstrating that the voltage activated K+ channel is present on peripheral T cells of miniswine and that blockade of Kv 1.3 inhibits both a delayed-type hypersensitivity reaction and an Ab response to an allogeneic challenge.
Identification and biochemical characterization of a novel nortriterpene inhibitor of the human lymphocyte voltage-gated potassium channel, Kv1.3.
Correolide is the first potent, small molecule inhibitor of Kv1 series channels to be identified from a natural product source and will be useful as a probe for studying potassium channel structure and the physiological role of such channels in target tissues of interest.
Identification of a new class of inhibitors of the voltage-gated potassium channel, Kv1.3, with immunosuppressant properties.
Data suggest that DSC derivatives represent a new class of immunosuppressant agents and that specific interactions of trans DSC analogues with channel conformations related to C-type inactivation may permit development of selective K(v)1.3 channel inhibitors useful for the safe treatment of autoimmune diseases.
Bis(benzylisoquinoline) analogs of tetrandrine block L-type calcium channels: evidence for interaction at the diltiazem-binding site.
Data indicate that a variety of bis(benzylisoquinoline) congeners act to block the L-type Ca2+ channel by binding to the benzothiazepine site on the channel.
Protein surface recognition by rational design: nanomolar ligands for potassium channels.
- S. Gradl, J. Felix, E. Isacoff, Maria L. Garcia, D. Trauner
- BiologyJournal of the American Chemical Society
- 22 October 2003
The rational design and development of four-fold symmetrical ligands for potassium channels is described.
Substitution of a single residue in Stichodactyla helianthus peptide, ShK-Dap22, reveals a novel pharmacological profile.
A large body of evidence is presented which indicates that the potencies of wild-type ShK peptide for both K( v)1.3 and K(v) 1.1 channels have been previously underestimated and suggests that ShK-Dap(22) will not have the same in vivo immunosuppressant efficacy of other K.3 blockers, such as margatoxin or ShK.
The inhibition of receptor-mediated and voltage-dependent calcium entry by the antiproliferative L-651,582.
Characterization of a new class of potent inhibitors of the voltage-gated sodium channel Nav1.7.
Members of the novel 1-benzazepin-2-one structural class of Nav1 blockers can display selectivity toward the peripheral nerve Nav1.7 channel subtype, and with appropriate pharmacokinetic and drug metabolism properties, these compounds could be developed as analgesic agents.
Binding of Correolide to the Kv1.3 Potassium Channel: Characterization of the Binding Domain by Site-Directed Mutagenesis†
Dihydrocorreolide binds with high affini affinity to the voltage-gated potassium channel Kv1.3 and acts as an immunosuppressant to mice with high IgG levels.
Margatoxin binds to a homomultimer of K(V)1.3 channels in Jurkat cells. Comparison with K(V)1.3 expressed in CHO cells.
The characteristics of [125I]MgTX binding, the antibody profiles, and the effects of the peptidyl K(V) channel inhibitors all indicate that the [ 125I] MgTX receptor in Jurkat lymphocytes is comprised of a homomultimer of K( V)1.3, unlike the heteromULTimeric arrangement of the receptor in rat brain.