Combinatorial synthesis of omega-conotoxin MVIIC analogues and their binding with N- and P/Q-type calcium channels.
Omega-conotoxin MVIIC (MVIIC) blocks P/Q-type calcium channels with high affinity and N-type calcium channels with low affinity, while the highly homologous omega-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 omega-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.
Sasaki
T
T
Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida-shi, Tokyo, Japan. sasaki@libra.ls.m-kagaku.co.jp
Kobayashi
K
K
Kohno
T
T
Sato
K
K
D000595:Amino Acid Sequence; D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D020650:Combinatorial Chemistry Techniques; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D051381:Rats; D020960:omega-Conotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC