Universidad Nacional AutÓnoma De MÉxico

University of Szeged

University of Debrecen

György Panyi

Lourival Domingos Possani-Postay

Lourival Domingos Possani Postay

Rezsö Gáspár

Zoltán S Varga

Zoltan Varga

César Vicente Ferreira Batista

Kinga Rakosi

Georgina Gurrola-Briones

Gabor Toth

Saida Patricia Salas-Castillo

Gábor TÓTH

Kinga RÁKOSI

Zoltán Varga

Cesar Vicente Ferreira Batista

The invention relates to toxin peptides capable of selectively inhibiting a Kv1.3 potassium channel protein. The toxin peptides of the invention are modified anuroctonus scorpion toxin peptides.

Modified peptide toxins

Potassium channels Kv1.3 are known to be implicated in immunological diseases and graft rejections. Disclosed are peptides capable of blocking with high affinity and specificity potassium channels Kv1.3, their pharmaceutical compositions, and methods for their use to block Kv1.3 potassium channels, to treat various immunological conditions and to diagnostic applications. Methods for their chemical synthesis and correct folding are also disclosed. Exemplary peptides correspond to protein components (Vm23 and Vm24) isolated from the venom of the Mexican scorpion. Vm23 and Vm24 bind to hKv1.3 channels in an almost irreversible manner, showing a Kd value in the order of 3 picomolar range, when applied to human lymphocytes cultures in vitro. Vm24 was chemically synthesized and used in in vivo experiments to successfully treat sensitized rats (on the DTH-response). Neither Vm24 nor synthetic Vm24 is toxic to mice when injected at relatively high concentrations (assayed up to 10,000 micrograms per kilogram mouse body weight). These peptides (Vm24 and Vm23) and their functional equivalent analogs with at least 83% of sequence identity are lead compounds, candidates for the treatment of various immunological conditions and diagnostic applications.

Vm23 and Vm24, two scorpion peptides that block human T-lymphocyte potassium channels (sub-type Kv1.3) with high selectivity and decrease the in vivo DTH-responses in rats

Growing community of inventors

Debrecen, Hungary

György Panyi