Synthesis and characterization of a disulfide bond isomer of omega-conotoxin GVIA.
Solid phase peptide synthesis and air oxidation of omega-conotoxin GVIA yielded, in addition to the desired product, an isomeric peptide which could be completely separated from the native toxin by repeated HPLC. A chymotrypsin-trypsin digest of this peptide, when subjected to HPLC peptide mapping, provided peptides identical with synthetic disulfide containing peptides predicted for the omega-conotoxin isomer containing C1-C2, C3-C5, C4-C6 cystinyl pairings. The 'shaking' potency (ED50 = 1500 pmoles/kg, i.c.v.) of the isomeric peptide upon cannulated rats was 1.3% of the potency of native conotoxin (ED50 = 20 pmoles/kg). Considering that all three disulfide pairings in the isomer are different from the native toxin, its retention of biological activity is of interest.
Pennington
M W
MW
Department of Peptide Chemistry, BACHEM Bioscience Inc., Philadelphia, PA 19104.
Festin
S M
SM
Maccecchini
M L
ML
Kem
W R
WR
D000595:Amino Acid Sequence; D000818:Animals; D008297:Male; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D020866:omega-Conotoxin GVIA
D010456:Peptides, Cyclic; D020866:omega-Conotoxin GVIA