Dutton Julie L, Bansal Paramjit S, Hogg Ron C, Adams David J, Alewood Paul F, Craik David J
Institute for Molecular Bioscience, Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
J Biol Chem. 2002 Dec 13;277(50):48849-57. doi: 10.1074/jbc.M208842200. Epub 2002 Oct 9.
alpha-Conotoxin AuIB and a disulfide bond variant of AuIB have been synthesized to determine the role of disulfide bond connectivity on structure and activity. Both of these peptides contain the 15 amino acid sequence GCCSYPPCFATNPDC, with the globular (native) isomer having the disulfide connectivity Cys(2-8 and 3-15) and the ribbon isomer having the disulfide connectivity Cys(2-15 and 3-8). The solution structures of the peptides were determined by NMR spectroscopy, and their ability to block the nicotinic acetylcholine receptors on dissociated neurons of the rat parasympathetic ganglia was examined. The ribbon disulfide isomer, although having a less well defined structure, is surprisingly found to have approximately 10 times greater potency than the native peptide. To our knowledge this is the first demonstration of a non-native disulfide bond isomer of a conotoxin exhibiting greater biological activity than the native isomer.
已合成α-芋螺毒素AuIB及其二硫键变体，以确定二硫键连接对结构和活性的作用。这两种肽均包含15个氨基酸序列GCCSYPPCFATNPDC，球状（天然）异构体的二硫键连接为Cys(2-8和3-15)，带状异构体的二硫键连接为Cys(2-15和3-8)。通过核磁共振光谱法测定了这些肽的溶液结构，并检测了它们阻断大鼠副交感神经节解离神经元上烟碱型乙酰胆碱受体的能力。令人惊讶的是，尽管带状二硫键异构体的结构不太明确，但发现其效力比天然肽高约10倍。据我们所知，这是首次证明芋螺毒素的非天然二硫键异构体比天然异构体具有更高的生物活性。
