Advertisement

If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.

ENJOY UNLIMITED ACCES TO C&EN

Materials

Synthetic Sodium Transporter

Covalently modified G-quadruplex moves sodium across lipid bilayer

by Celia Henry Arnaud
January 2, 2006 | A version of this story appeared in Volume 84, Issue 1

ION SHUTTLE
[+]Enlarge
Credit: ADAPTED FROM J. AM. CHEM. SOC.
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.
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.

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.

Advertisement

Article:

This article has been sent to the following recipient:

0 /1 FREE ARTICLES LEFT THIS MONTH Remaining
Chemistry matters. Join us to get the news you need.