NEW PEPTIDE VARIANTS WITH ANALGESIC ACTIVITY DERIVED FROM RECOMBINANT NEUROTOXINS

Abstract

The present invention relates to obtaining novel recombinant peptide variants, generated by heterologous expression in E. coli, with antinociceptive (analgesic) activity, particularly in mammals. These peptide variants were derived from the recombinant toxin HisrCssII-RCR (SEQ. ID NO: 1), based on computational structural biology studies conducted by the inventors of the present invention, as well as on sequence information from the CeII8 toxin of the scorpion Centruroides elegans. The peptide variants of the present invention comprise the variants named: HisrCssII-TCD (SEQ. ID NO: 2) and HisrCssII-Del-A-TCD (SEQ. ID NO: 3); which did not exhibit toxicity in the murine model (see example 6). The peptide variants of the present invention exhibited antinociceptive activity, the HisrCssII-Del-A-TCD variant being (SEQ.ID NO: 3) which exhibited the greatest effect, comparable to a positive analgesic control (DAMGO). On the other hand, the HisrCssII-Del-A-TCD variant (SEQ. ID NO: 3) exhibited an analgesic effect in inflammatory and neuropathic pain models. The invention also relates to DNA fragments encoding such variants, molecular vectors for their expression, bacterial cells transformed with such vectors capable of producing the variant peptides, and pharmaceutical compositions comprising said peptides.