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

Potassium channels KvI.3 are known to be implicated in immunological dise ases and graft rejections. Disclosed are peptides capable of blocking with h igh affinity and specificity potassium channels KvI.3, their pharmaceutical compositions, and methods for their use to block KvI .3 potassium channels, to treat various immunological conditions and to diagnostic applications. Me thods for their chemical synthesis and correct folding are also disclosed. E xemplary peptides correspond to protein components (Vm23 and Vm24) isolated from the venom of the Mexican scorpion Vaejovis mexicanus smithi. Vm23 and V m24 bind to hKvl.3 channels in an almost irreversible manner, showing a Kd v alue in the order of 3 picomolar range, when applied to human lymphocytes cu ltures in vitro. Vm24 was chemically synthesized and used in in vivo experim ents to successfully treat sensitized rats (on the DTH-response). Neither Vm 24 nor synthetic Vm24 is toxic to mice when injected at relatively high conc entrations (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 tr eatment of various immunological conditions and diagnostic applications.