Combinatorial synthesis of ω‐conotoxin MVIIC analogues and their binding with N‐ and P/Q‐type calcium channels

FEBS Letters

Kobayashi, Kuniko¹  Sasaki, Toru¹  Sato, Kazuki¹  Kohno, Toshiyuki¹ 

[1] Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida-shi, Tokyo 194-8511, Japan

关键词: ω-Conotoxin MVIIC;    Calcium channel;    Disulfide bond;    Combinatorial synthesis;    Fmoc;    9-fluorenylmethoxycarbonyl;    GVIA;    ω-conotoxin GVIA;    HPLC;    high-performance liquid chromatography;    HEPES;    N-(2-hydroxyethyl)piperazine-N′-ethanesulfonic acid;    MALDI-TOF-MS;    matrix-assisted laser desorption/ionization time-of-flight mass spectrometry;    MVIIA;    ω-conotoxin MVIIA;    MVIIC;    ω-conotoxin MVIIC;    NMR;    nuclear magnetic resonance;    ODS;    octadecylsilane;   

DOI  :  10.1016/S0014-5793(99)01772-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

ω-Conotoxin MVIIC (MVIIC) blocks P/Q-type calcium channels with high affinity and N-type calcium channels with low affinity, while the highly homologous ω-conotoxin MVIIA blocks only N-type calcium channels. We wished to obtain MVIIC analogues more selective for P/Q-type calcium channels than MVIIC to elucidate structural differences among the channels, which discriminate the ω-conotoxins. To prepare a number of MVIIC analogues efficiently, we developed a combinatorial method which includes a random air oxidation step. Forty-seven analogues were prepared in six runs and some of them exhibited higher selectivity for P/Q-type calcium channels than MVIIC in binding assays.

【 授权许可】

Unknown