Interaction of alpha-conotoxin peptides with neuronal...

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 7/08 (2006.01) C07K 14/435 (2006.01) G01N 24/08 (2006.01) G01N 33/566 (2006.01) G01N 33/574 (2006.01) G01N 33/68 (2006.01) G06F 17/30 (2006.01) G06F 19/00 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2308115

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

L'invention concerne des dérivés du conopeptide MII, peptide de conotoxine d'.alpha.-4/7, dans lequel des résidus aminoacides sont substitués, selon l'invention, tout en conservant l'activité de base de MII. Elle concerne également la découverte de la structure tridimensionnelle de MII et le rapport entre sa structure et sa spécificité pour le sous-type .alpha.3.beta.2 du récepteur neural d'acétylcholine nicotinique (nAChR). Elle concerne également des programmes informatisés servant à l'expression de la structure tridimensionnelle de MII et de ses analogues peptidiques, ses mimétiques peptidiques ou non peptidiques. On peut mettre en corrélation les caractéristiques structurales avec l'activité biologique afin de pouvoir élaborer des analogues et des mimétiques de peptide de conotoxine .alpha.-4/7 qui montrent la même spécificité pour nAChR neural. Ces analogues et ces mimétiques sont utiles en tant qu'agents cardio-vasculaires et servent également à traiter ou à détecter le carcinome pulmonaire à petites cellules (SCLC).

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