Solution synthesis of charybdotoxin (ChTX), a K+ channel blocker.
Charybdotoxin, a 37 amino acid peptide which is a minor component of Leiurus quinquestriatus venom, was synthesized by the solution procedure applying our maximum protection strategy. After formation of the three disulfide bonds, for which a redox buffer was necessary, the final product was purified to homogeneity and found to have similar biological potency to that reported by others for the natural product. The disulfide bond configuration was found to be: Cys7-Cys28; Cys13-Cys33; Cys17-Cys35. Conformational analysis by 1H-NMR showed that the molecule exists as a very tightly folded structure, in which residues 1-7 and 24-37 form a triple-stranded beta-sheet, with a turn at positions 30-31. The region from 11-20 appears to adopt an alpha-helical conformation.
Peptide Institute Inc., Protein Research Foundation, Osaka, Japan.
P
P
Lambert
H
H
Kuroda
N
N
Chino
T X
TX
Watanabe
T
T
Kimura
S
S
Sakakibara
D000595:Amino Acid Sequence; D002021:Buffers; D018999:Charybdotoxin; D002851:Chromatography, High Pressure Liquid; D002918:Chymotrypsin; D004220:Disulfides; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D015221:Potassium Channels / Q000187:drug effects*; D011487:Protein Conformation; D012604:Scorpion Venoms / Q000138:chemical synthesis* / Q000494:pharmacology; D012996:Solutions
D002021:Buffers; D004220:Disulfides; D015221:Potassium Channels; D012604:Scorpion Venoms; D012996:Solutions; D018999:Charybdotoxin; D002918:Chymotrypsin