Synthetic Sodium Transporter | January 2, 2006 Issue - Vol. 84 Issue 1 | Chemical & Engineering News
Volume 84 Issue 1 | p. 10 | News of The Week
Issue Date: January 2, 2006

Synthetic Sodium Transporter

Covalently modified G-quadruplex moves sodium across lipid bilayer
Department: Science & Technology
News Channels: Biological SCENE, JACS In C&EN
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ION SHUTTLE
Monomers consisting of modified guanosine (left), templated by potassium ions (blue), self-assemble into a noncovalent G-quadruplex, which is modified via olefin metathesis into a unimolecular G-quadruplex (right). The covalent G-quadruplex acts as a sodium transporter.
Credit: ADAPTED FROM J. AM. CHEM. SOC.
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ION SHUTTLE
Monomers consisting of modified guanosine (left), templated by potassium ions (blue), self-assemble into a noncovalent G-quadruplex, which is modified via olefin metathesis into a unimolecular G-quadruplex (right). The covalent G-quadruplex acts as a sodium transporter.
Credit: ADAPTED FROM J. AM. CHEM. SOC.

Researchers have taken a step closer to a new type of synthetic ion channel with a G-quadruplex that acts as a sodium transporter (J. Am. Chem. Soc. 2006, 128, 38). Such transporters could eventually serve as sensors or antimicrobial agents.

G-quadruplexes are guanine-rich structures that bind metal cations. They are usually made of nucleic acids, but such hydrophilic structures aren't stable in the hydrophobic environment of a phospholipid membrane. A team led by Jeffery T. Davis, a professor of chemistry and biochemistry at the University of Maryland, makes guanosine—the combination of the base guanine and the sugar ribose—lipophilic by adding side chains to the ribose, but such modifications alone aren't enough.

"For three or four years, we've been trying to make ion channels by assembling lipophilic guanosine derivatives into G-quadruplex structures," Davis says. "Although they're stable in organic solvents, they don't seem to have the properties we want in a membrane."

Grad student Mark S. Kaucher and Davis achieve the function they want by adding polymerizable groups—allyl ethers—to the ribose. Templated by potassium ions, 16 monomers of the guanosine derivative form a noncovalent assembly of four G-quartet layers of four monomers each. The entire structure is stitched together via olefin metathesis within and between the layers of G-quartets. "Instead of being 16 molecules, it's one molecule," Davis says. "It can't fall apart."

When the team puts the "unimolecular" structure in a phospholipid membrane, the assembly moves sodium ions from outside to inside a liposome. They don't know yet how the transporter works—whether it is a channel with a pore or simply a carrier.

Shankar Balasubramanian of the University of Cambridge, who also works with modified G-quadruplexes, says, "This elegant study is, to the best of my knowledge, the first experimental demonstration" that G-quadruplexes could be used as ion channels.

 
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