Conotoxin GI: disulfide bridges, synthesis, and preparation of iodinated derivatives.

作者: WR Gray , TA Luque , R Galyean , E Atherton , RC Sheppard

DOI: 10.1021/BI00307A040

关键词:

摘要: The 13 amino acid toxic peptide from the marine snail Conus geographus, conotoxin GI, blocks acetylcholine receptor at neuromuscular junction. In this report, we describe a method for analyzing disulfide bonding in nanomole amounts of small cystine-rich peptides. procedure involves partial reduction and double-label alkylation cysteine residues. Using method, show that natural GI has (2-7, 3-13) configuration. structure been confirmed by chemical synthesis. preparation purification molecularly homogeneous, iodinated derivatives toxin are also described. All derivatives, including [diiodohistidine,diiodotyrosine]conotoxin retained least half biological activity unmodified toxin. Since tetraiodinated toxin, which is greater than 25% weight iodine, retains considerable toxicity, histidine tyrosine residues not crucial activity.

参考文章(20)
A. P. Ryle, F. Sanger, Disulphide interchange reactions Biochemical Journal. ,vol. 60, pp. 535- 540 ,(1955) , 10.1042/BJ0600535
E. Karlsson, Chemistry of Protein Toxins in Snake Venoms Springer Berlin Heidelberg. pp. 159- 212 ,(1979) , 10.1007/978-3-642-66913-2_5
J. Ken McDonald, Paul X. Callahan, Stanley Ellis, [22] Preparation and specificity of dipeptidyl aminopeptidase I Methods in Enzymology. ,vol. 25, pp. 272- 281 ,(1972) , 10.1016/S0076-6879(72)25024-8
W.R. Gray, [12] Dansyl chloride procedure Methods in Enzymology. ,vol. 11, pp. 139- 151 ,(1967) , 10.1016/S0076-6879(67)11014-8
W R Gray, J E Rivier, R Galyean, L J Cruz, B M Olivera, Conotoxin MI. Disulfide bonding and conformational states. Journal of Biological Chemistry. ,vol. 258, pp. 12247- 12251 ,(1983) , 10.1016/S0021-9258(17)44165-2
Paul X. Callahan, J. Ken McDonald, Stanley Ellis, [23] Sequencing of peptides with dipeptidyl aminopeptidase I Methods in Enzymology. ,vol. 25, pp. 282- 298 ,(1972) , 10.1016/S0076-6879(72)25025-X
W.R. Gray, A. Luque, B.M. Olivera, J. Barrett, L.J. Cruz, Peptide toxins from Conus geographus venom. Journal of Biological Chemistry. ,vol. 256, pp. 4734- 4740 ,(1981) , 10.1016/S0021-9258(19)69313-0
E. Atherton, M.J. Gait, R.C. Sheppard, B.J. Williams, The polyamide method of solid phase peptide and oligonucleotide synthesis Bioorganic Chemistry. ,vol. 8, pp. 351- 370 ,(1979) , 10.1016/0045-2068(79)90062-2