Maurotoxin, PI1 and HSTX1 derivatives

Details Maurotoxin, PI1 and HSTX1 derivatives Maurotoxin, PI1 and HSTX1 derivatives

2008-01-22

2010-11-09

Tsang, Cecilia (Department: 1654)

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

Cyclic peptides

Reexamination Certificate

active

07829666

ABSTRACT:
Derivatives of Maurotoxin (MTX) in which the native disulfide bridge pattern (Cys3-Cys24, Cys9-Cys29, Cys19, Cys31-Cys34) has been disrupted are useful for the treatment of pathologies associated with dysfunctioning and/or activation of Ca2+-activated and/or voltage-gated K+channel subtypes, such as IKCa1 or Kv1.2. In one group of derivatives, one or two of the amino acid residues of maurotoxin have been replaced by different amino acid residues resulting in the disulfide bridge pattern being changed to Cys3-Cys24, Cys9-Cys29, Cys13-Cys31, Cys19-Cys34. Exemplary substitutions include the Arg residue at position 14 and/or the Lys residue at position 15 replaced by a Gln residue and the Gly residue at position 33 replaced by an Ala residue. Pi1 and HsTx1 derivatives with disrupted native disulfide bridge patterns are similarly useful.

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