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 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,...
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creator | GURROLA-BRIONES GEORGINA SALAS-CASTILLO SAIDA PATRICIA FERREIRA BATISTA CESAR VICENTE POSSANI POSTAY LOURIVAL DOMINGOS GASPAR REZSOE PANYI GYOERGY VARGA ZOLTAN S |
description | 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 Vaejovis mexicanus smithi. 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 microgr |
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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 Vaejovis mexicanus smithi. 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). 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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 Vaejovis mexicanus smithi. 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 microgr</abstract><oa>free_for_read</oa></addata></record> |
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subjects | CHEMISTRY HUMAN NECESSITIES HYGIENE INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES MEASURING MEDICAL OR VETERINARY SCIENCE METALLURGY ORGANIC CHEMISTRY PEPTIDES PHYSICS PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS TESTING |
title | 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 |
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