Solid-phase synthesis and biological activity of a thioether analogue of conotoxin G1.
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Solid-phase synthesis and biological activity of a thioether analogue of conotoxin G1. / Bondebjerg, Jon; Grunnet, Morten; Jespersen, Thomas; Meldal, Morten.
In: ChemBioChem, Vol. 4, No. 2-3, 2003, p. 186-94.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Solid-phase synthesis and biological activity of a thioether analogue of conotoxin G1.
AU - Bondebjerg, Jon
AU - Grunnet, Morten
AU - Jespersen, Thomas
AU - Meldal, Morten
N1 - Keywords: Animals; Chromatography, High Pressure Liquid; Conotoxins; Cyclization; Female; Oocytes; Peptide Biosynthesis; Receptors, Nicotinic; Structure-Activity Relationship; Sulfides; Xenopus
PY - 2003
Y1 - 2003
N2 - A bicyclic thioether analogue of alpha-conotoxin G1, a neurotoxin found in the venom of cone snails, was synthesized on solid phase. Two successive intramolecular on-bead cyclizations between a cysteine residue and a chloroacetylated reduced peptide bond are the key steps in the synthesis. The first reduced peptide bond was introduced by a reductive alkylation with a 9-fluorenylmethoxycarbonyl protected amino aldehyde, and the second by coupling of a dipeptide building block containing an allyloxycarbonyl protected reduced peptide bond. The desired bicyclic product was obtained as a mixture of two isomers, which were evaluated for their ability to inhibit the muscular nicotinic acetylcholine receptor expressed in Xenopus oocytes. The two isomers were found to have IC(50) values (inhibitory activities) of 144 microM and 48 microM, compared to 0.18 microM for native conotoxin G1.
AB - A bicyclic thioether analogue of alpha-conotoxin G1, a neurotoxin found in the venom of cone snails, was synthesized on solid phase. Two successive intramolecular on-bead cyclizations between a cysteine residue and a chloroacetylated reduced peptide bond are the key steps in the synthesis. The first reduced peptide bond was introduced by a reductive alkylation with a 9-fluorenylmethoxycarbonyl protected amino aldehyde, and the second by coupling of a dipeptide building block containing an allyloxycarbonyl protected reduced peptide bond. The desired bicyclic product was obtained as a mixture of two isomers, which were evaluated for their ability to inhibit the muscular nicotinic acetylcholine receptor expressed in Xenopus oocytes. The two isomers were found to have IC(50) values (inhibitory activities) of 144 microM and 48 microM, compared to 0.18 microM for native conotoxin G1.
U2 - 10.1002/cbic.200390030
DO - 10.1002/cbic.200390030
M3 - Journal article
C2 - 12616632
VL - 4
SP - 186
EP - 194
JO - ChemBioChem
JF - ChemBioChem
SN - 1439-4227
IS - 2-3
ER -
ID: 8419043