title: Synthesis and biological evaluation of an iodinated iberiotoxin analogue, [mono-iodo-Tyr5, Phe36]-iberiotoxin.
abstract: The synthesis and iodination of a structural analogue of the specific large-conductance calcium-activated potassium (BK) channel blocker, iberiotoxin (IbTX), a 37-amino acid scorpion neurotoxin, is reported. The synthesis of this analogue, [Tyr5, Phe36]-IbTX, was accomplished using standard solid-phase Fmoc (9-fluorenylmethoxycarbonyl) chemistry protocols. The linear peptide was cyclized via the formation of three intramolecular disulfide bridges and subsequently iodinated at the Tyr5 position. Upon purification, the iodinated analogue, [mono-iodo-Tyr5, Phe36]-IbTX, exhibited comparable biological activity to native IbTX in blocking BK-mediated currents. These findings suggest the synthesis and use of an 125I labelled IbTX analogue for BK channel localization in autoradiography experiments.
authors.affiliation: Department of Central Nervous System Chemistry, Richard L. Gelb Center for Pharmaceutical Research and Development, Bristol-Myers Squibb, Wallingford, Connecticut, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Kozlowski
authors.forename: G
authors.initials: G
authors.lastname: Johnson
authors.forename: D D
authors.initials: DD
authors.lastname: Dischino
authors.forename: S I
authors.initials: SI
authors.lastname: Dworetzky
authors.forename: C G
authors.initials: CG
authors.lastname: Boissard
authors.forename: V K
authors.initials: VK
authors.lastname: Gribkoff
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D011994:Recombinant Proteins / Q000187:drug effects; D012604:Scorpion Venoms / Q000737:chemistry*; D014981:Xenopus
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D015221:Potassium Channels; D011994:Recombinant Proteins; D012604:Scorpion Venoms; C103121:iodo-Tyr(5)-Phe(36)-iberiotoxin