Synthesis of omega-agatoxin IVA and its related peptides.
A potent and selective P type calcium channel blocker isolated from the venom of the funnel web spider Agelenopsis aperta, omega-agatoxin IVA, and its related peptides were synthesized by the solution procedure. Synthetic omega-agatoxin IVA was found to block high-threshold P-type calcium current in rat Purkinje neuron with the same potency as that reported for the natural product. Its disulfide structure was determined by amino acid analysis, gas-phase sequencing and mass spectrometry of the proteolytic fragments. The N-terminus biotinylated and truncated peptides showed the same disulfide-bond-forming profile and the same activities as those of omega-agatoxin IVA, indicating that the N-terminal basic tripeptide, Lys-Lys-Lys, is not important for both the folding and the expression of the biological activity. However, the Trp residue in the molecule might be essential for the toxin to bind tightly with the channel pores.
Nishio
H
H
Peptide Institute, Inc., Protein Research Foundation, Osaka, Japan.
Kumagaye
K Y
KY
Kubo
S
S
Chen
Y N
YN
Momiyama
A
A
Takahashi
T
T
Kimura
T
T
Sakakibara
S
S
D000595:Amino Acid Sequence; D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D004220:Disulfides; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013111:Spider Venoms / Q000138:chemical synthesis* / Q000494:pharmacology; D013997:Time Factors; D020867:omega-Agatoxin IVA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004220:Disulfides; D007202:Indicators and Reagents; D010446:Peptide Fragments; D013111:Spider Venoms; D020867:omega-Agatoxin IVA