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.

引用

收藏

页码：3193 / 3196

页数：4

相关论文

共 23 条

[11]

Chandy KG, 2001, TOXICON, V39, P1269, DOI 10.1016/S0041-0101(01)00120-9

[12] Recent developments in the biology and medicinal chemistry of potassium channel modulators: Update from a decade of progress [J].

Coghlan, MJ ;

Carroll, WA ;

Gopalakrishnan, M .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (11) :1627-1653

[13] Diprotected triflylguanidines: A new class of guanidinylation reagents [J].

Feichtinger, K ;

Zapf, C ;

Sings, HL ;

Goodman, M .

JOURNAL OF ORGANIC CHEMISTRY, 1998, 63 (12) :3804-3805

[14] Identification and biochemical characterization of a novel nortriterpene inhibitor of the human lymphocyte voltage-gated potassium channel, Kv1.3 [J].

Felix, JP ;

Bugianesi, RM ;

Schmalhofer, WA ;

Borris, R ;

Goetz, MA ;

Hensens, OD ;

Bao, JM ;

Kayser, F ;

Parsons, WH ;

Rupprecht, K ;

Garcia, ML ;

Kaczorowski, GJ ;

Slaughter, RS .

BIOCHEMISTRY, 1999, 38 (16) :4922-4930

[15] PYRROLE STUDIES .22. [4-PI + 2-PI] CYCLOADDITION REACTIONS WITH VINYLPYRROLES [J].

JONES, RA ;

MARRIOTT, MTP ;

ROSENTHAL, WP ;

SEPULVEDAARQUES, J .

JOURNAL OF ORGANIC CHEMISTRY, 1980, 45 (22) :4515-4519

[16]

Kem WR, 1999, PERSPECT DRUG DISCOV, V16, P111

[17] Synthesis of substituted indoles via a highly selective 7-lithiation of 4,7-dibromoindoles and the effect of indole-nitrogen on regioselectivity [J].

Li, LH ;

Martins, A .

TETRAHEDRON LETTERS, 2003, 44 (32) :5987-5990

[18] Potassium channel blockade by the sea anemone toxin ShK for the treatment of multiple sclerosis and other autoimmune diseases [J].

Norton, RS ;

Pennington, MW ;

Wulff, H .

CURRENT MEDICINAL CHEMISTRY, 2004, 11 (23) :3041-3052

[19] Identification of three separate binding sites on SHK toxin, a potent inhibitor of voltage-dependent potassium channels in human T-lymphocytes and rat brain [J].

Pennington, MW ;

Mahnir, VM ;

Krafte, DS ;

Zaydenberg, I ;

Byrnes, ME ;

Khaytin, I ;

Crowley, K ;

Kem, WR .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 219 (03) :696-701

[20] Structural conservation of the pores of calcium-activated and voltage-gated potassium channels determined by a sea anemone toxin [J].

Rauer, H ;

Pennington, M ;

Cahalan, M ;

Chandy, KG .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (31) :21885-21892