INTERACTION OF ALPHA-CONOTOXIN PEPTIDES WITH NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS

摘要

This invention relates to derivatives of the conopeptide MII, an .alpha.-4/7conotoxin peptide, in which amino acid residues are substituted as describedherein while maintaining the basic activity of MII. The present invention alsorelates to the discovery of the 3-dimensional structure of MII, and therelationship of its structure to its specificity to the .alpha.3.beta.2subtype of the neuronal nicotinic acetylcholine receptor (nAChR). The presentinvention also relates to computer based programs for the expression of thethree-dimensional structure of MII and peptide analogs, peptide mimetics ornon-peptide mimetics thereof. The structural characteristics may be correlatedwith biological activity to enable the design of .alpha.-4/7 conotoxin peptideanalogs and peptide mimetics which demonstrate the same specificity toneuronal nAChR. Such analogs and peptide mimetics are useful as cardiovascularagents and for treating or detecting small-cell lung carcinoma (SCLC).