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Chemical control of metabolically-engineered voltage-gated K+ channels.


ABSTRACT: Metabolic oligosaccharide engineering is a powerful approach for installing unnatural glycans with unique functional groups into the glycocalyx of living cells and animals. Using this approach, we showed that K(+) channel complexes decorated with thiol-containing sialic acids were irreversibly inhibited with scorpion toxins bearing a pendant maleimide group. Irreversible inhibition required a glycosylated K(+) channel subunit and was completely reversible with mild reductant when the tether connecting the toxin to the maleimide contained a disulfide bond. Cleavage of the disulfide bond not only restored function, but delivered a biotin moiety to the modified K(+) channel subunit, providing a novel approach for preferentially labeling wild type K(+) channel complexes functioning in cells.

SUBMITTER: Hua Z 

PROVIDER: S-EPMC3156388 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Chemical control of metabolically-engineered voltage-gated K+ channels.

Hua Zhengmao Z   Lvov Anatoli A   Morin Trevor J TJ   Kobertz William R WR  

Bioorganic & medicinal chemistry letters 20110428 17


Metabolic oligosaccharide engineering is a powerful approach for installing unnatural glycans with unique functional groups into the glycocalyx of living cells and animals. Using this approach, we showed that K(+) channel complexes decorated with thiol-containing sialic acids were irreversibly inhibited with scorpion toxins bearing a pendant maleimide group. Irreversible inhibition required a glycosylated K(+) channel subunit and was completely reversible with mild reductant when the tether conn  ...[more]

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