Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence
Patent
1993-07-16
1997-01-07
Weimar, Elizabeth C.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
25 or more amino acid residues in defined sequence
C07K 1400, C07K 700, A61K 3800
Patent
active
055918212
ABSTRACT:
The present invention is directed to .omega.-conotoxin peptides having 24-30 amino acids, six cysteines which form disulfide bonds between the first and fourth, second and fifth, and third and sixth cysteines, respectively, and an internal sequence of Cys-Arg-Lys-Thr-Xaa.sub.1 -Tyr-Xaa.sub.2 -Cys-Cys-Ser-Gly-Ser-Cys (SEQ ID NO:1). The invention is further directed to .omega.-conotoxin peptides of the generic formula Cys-Xaa.sub.1 -Gly-Xaa.sub.2 -Gly-Ala-Xaa.sub.3 -Cys-Arg-Lys-Thr-Xaa.sub.4 -Tyr-Xaa.sub.5 -Cys-Cys-Ser-Gly-Ser-Cys-Xaa.sub.6 -Arg-Gly-Xaa.sub.7 -Cys (SEQ ID NO:2). Preferably, the C-terminus is amidated. These peptides also contain three disulfide bonds. Examples of .omega.-conotoxin peptides within the generic formula are MVIIC having the formula Cys-Cys-Gly-Lys-Gly-Ala-Xaa.sub.1 -Cys-Arg-Lys-Thr-Xaa.sub.2 -Tyr-Asp-Cys-Cys-Ser-Gly-Ser-Cys-Gly-Arg-Arg-Gly-Lys-Cys (SEQ ID NO:3), wherein Xaa is preferably Pro or Hyp (4-hydroxyproline) and Xaa.sub.2 is preferably Met or Nle (norleucine) and wherein preferably the C-terminus is amidated, and MVIID having the formula Cys-Gln-Gly-Arg-Gly-Ala-Ser-Cys-Arg-Lys-Thr-Xaa-Tyr-Asn-Cys-Cys-Ser-Gly-Se r-Cys-Asn-Arg-Gly-Arg-Cys (SEQ ID NO:4), wherein Xaa is preferably Met or Nle (norleucine), and wherein preferably the C-terminus is amidated. These peptides target the P-like subtypes of Ca.sup.2+ channels as well as the N-type Ca.sup.2+ channels.
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Hillyard David R.
Imperial Julita S.
Monje Virginia D.
Olivera Baldomero M.
Marshall S. G.
The University of Utah
Weimar Elizabeth C.
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