Synthesis of [Cys(5)]mu-conotoxin GIIIA and its derivatives as a probe of Na(+) channel analysis.
The residue of Thr-5 in mu-conotoxin GIIIA (GIIIA), a receptor site I sodium channel blocker, was replaced with Cys. The synthesized [Cys(5)]GIIIA had a similar 3D structure to the native GIIIA, revealed by CD and NMR. [Cys(5)]GIIIA and its tagged peptides inhibited the electrically stimulated contraction of the rat diaphragm with relatively comparable potency to that of GIIIA. Since the contractile response to electrical stimuli is caused by the activation of sodium channels, [Cys(5)]GIIIA could be a prototype for synthesizing useful tools for the analysis of sodium channels. Thus, [Cys(5)]GIIIA could be a prototype for synthesizing useful tools for the analysis of sodium channels.
Nakamura
M
M
Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa-ku, Nagoya, 464-8601, Japan. i99301d@mbox.media.nagoya-u.ac.jp
Ishida
Y
Y
Kohno
T
T
Sato
K
K
Nakamura
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D020916:Conotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000032:analysis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D020916:Conotoxins; D015335:Molecular Probes; D015222:Sodium Channels; C046101:conotoxin GIII