A three-residue, continuous binding epitope peptidomimetic of ShK toxin as a Kv1.3 inhibitor

被引：18

作者：

Harvey, AJ

Gable, RW

Baell, JB

机构：

[1] Walter & Eliza Hall Inst Med Res, Ctr Biotechnol, Bundoora, Vic 3086, Australia

[2] Univ Melbourne, Sch Chem, Melbourne, Vic 3010, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 13期

关键词：

peptidomimetic; indole; Kv1.3; ion channel; multiple sclerosis;

D O I：

10.1016/j.bmcl.2005.05.014

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The ShK toxin is a polypeptide that blocks the Kv1.3 potassium channel in T-lymphocytes and has been identified as a potential therapeutic for multiple sclerosis. ShK is well characterised in terms of structure and binding, offering an attractive target for the design of structural and functional mirnetics. Building on our previous success in developing rationally designed peptidomimetics of ShK, we report a novel mimetic of the K22 Y23-R24 residues of the peptide. The mimetic was shown to inhibit the Kv1.3 channel with moderate activity. (c) 2005 Elsevier Ltd. All rights reserved.

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收藏

页码：3193 / 3196

页数：4

相关论文

共 23 条

[1] Synthesis and biological evaluation of nonpeptide mimetics of co-conotoxin GVIA [J].

Baell, JB ;

Duggan, PJ ;

Forsyth, SA ;

Lewis, RJ ;

Lok, YP ;

Schroeder, CI .

BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (15) :4025-4037

[2] Khellinone derivatives as blockers of the voltage-gated potassium channel Kv1.3:: Synthesis and immunosuppressive activity [J].

Baell, JB ;

Gable, RW ;

Harvey, AJ ;

Toovey, N ;

Herzog, T ;

Hänsel, W ;

Wulff, H .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (09) :2326-2336

[3] ω-conotoxins and approaches to their non-peptide mimetics [J].

Baell, JB ;

Duggan, PJ ;

Lok, YP .

AUSTRALIAN JOURNAL OF CHEMISTRY, 2004, 57 (03) :179-185

[4] Design and synthesis of type-III mimetics of ω-conotoxin GVIA [J].

Baell, JB ;

Forsyth, SA ;

Gable, RW ;

Norton, RS ;

Mulder, RJ .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2001, 15 (12) :1119-1136

[5]

Baell JB, 2002, J COMPUT AID MOL DES, V16, P245, DOI 10.1023/A:1016310602813

[6] Potent Kv1.3 inhibitors from correolide - modification of the C18 position [J].

Bao, JM ;

Miao, SW ;

Kayser, F ;

Kotliar, AJ ;

Baker, RK ;

Dossa, GA ;

Felix, JP ;

Bugianesi, RM ;

Slaughter, RS ;

Kaczorowski, GJ ;

Garcia, ML ;

Ha, SN ;

Castonguay, L ;

Koo, GC ;

Shah, K ;

Springer, MS ;

Staruch, MJ ;

Parsons, WH ;

Rupprecht, KM .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (02) :447-451

[7] Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases [J].

Beeton, C ;

Pennington, MW ;

Wulff, H ;

Singh, S ;

Nugent, D ;

Crossley, G ;

Khaytin, I ;

Calabresi, PA ;

Chen, CY ;

Gutman, GA ;

Chandy, KG .

MOLECULAR PHARMACOLOGY, 2005, 67 (04) :1369-1381

[8] Selective blockade of T lymphocyte K+ channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis [J].

Beeton, C ;

Wulff, H ;

Barbaria, J ;

Clot-Faybesse, O ;

Pennington, M ;

Bernard, D ;

Cahalan, MD ;

Chandy, KG ;

Béraud, E .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :13942-13947

[9] Ion channels in the immune system as targets for immunosuppression [J].

Cahalan, MD ;

Chandy, KG .

CURRENT OPINION IN BIOTECHNOLOGY, 1997, 8 (06) :749-756

[10] K+ channels as targets for specific immunomodulation [J].

Chandy, KG ;

Wulff, H ;

Beeton, C ;

Pennington, M ;

Gutman, GA ;

Cahalan, MD .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2004, 25 (05) :280-289