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XB-ART-38446
Proc Natl Acad Sci U S A 2008 Aug 05;10531:10774-8. doi: 10.1073/pnas.0802850105.
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Engineered specific and high-affinity inhibitor for a subtype of inward-rectifier K+ channels.

Ramu Y , Xu Y , Lu Z .


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Inward-rectifier K(+) (Kir) channels play many important biological roles and are emerging as important therapeutic targets. Subtype-specific inhibitors would be useful tools for studying the channels' physiological functions. Unfortunately, available K(+) channel inhibitors generally lack the necessary specificity for their reliable use as pharmacological tools to dissect the various kinds of K(+) channel currents in situ. The highly conserved nature of the inhibitor targets accounts for the great difficulty in finding inhibitors specific for a given class of K(+) channels or, worse, individual subtypes within a class. Here, by modifying a toxin from the honey bee venom, we have successfully engineered an inhibitor that blocks Kir1 with high (1 nM) affinity and high (>250-fold) selectivity over many commonly studied Kir subtypes. This success not only yields a highly desirable tool but, perhaps more importantly, demonstrates the practical feasibility of engineering subtype-specific K(+) channel inhibitors.

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References [+] :
Boim, ROMK inwardly rectifying ATP-sensitive K+ channel. II. Cloning and distribution of alternative forms. 1995, Pubmed, Xenbase