New peptide substrates for botulinum toxin type A, useful in screening for therapeutic toxin inhibitors and for in vitro detection of the toxin

摘要

A peptide substrate (I) that is recognized selectively by botulinum toxin type A, is new. A peptide substrate (I) that is recognized selectively by botulinum toxin type A is new. It includes the motif Nop-Z-Pya that is cleaved by the toxin, where Nop is L-(p-nitro)phenylalanine, Pya is L-pyrenylalanine and Z is an amino acid sequence of 2-4 amino acids (preferably 2 amino acids). Independent claims are also included for: (1) metabolites (II) formed by cleavage of (I) by botulinum toxin type A, which are non-fluoresent if they contain Nop or fluorescent if they contain Pya; (2) detecting, identifying and/or measuring compounds that inhibit botulinum toxin type A; (3) in vitro detection of botulinum toxin type A in a biological sample; and (4) kits that contain (I), optionally also botulinum toxin type A and reagents for detecting the toxin and its inhibitors. ACTIVITY : Antidote. MECHANISM OF ACTION : Botulinum toxin type A inhibitor; Metalloprotease inhibitor.