Science Concentrates: ACS meeting news ▸ Nanoparticles to diagnose and treat atherosclerosis Researchers have developed nanoparticles that localize to arterial plaques and provide a possible new means to diagnose and treat atherosclerosis. Early detection of atherosclerosis is difficult and effective therapies are not available, making the condition a common cause of death worldwide. Plaques that are the hallmark of the disease form when white blood cells called macrophages attract cholesterol and agglomerate in arteries. These buildups can cause heart attacks, and when macrophages die, they can cause plaques to rupture and block blood flow, potentially causing strokes. High-density lipoprotein (HDL, or “good cholesterol”) deters This nanoparticle plaque formation by was designed promoting transport for diagnosis of cholesterol from and treatment of plaques to the liver atherosclerotic for excretion. In 2013, plaques; some Shanta Dhar’s group components are at the University of not labeled. Georgia reported the
OUTREACH
A scene from San Diego This budding chemist tried his hand at pencil electrolysis during the ACS national meeting’s presidential outreach event, held in conjunction with the San Diego Festival of Science & Engineering. In this demo, two pencils, serving as electrodes, are hooked up to a battery and dunked into water. The current that runs through the pencils’ graphite breaks down the water, forming bubbles of oxygen at one pencil tip and bubbles of hydrogen at the other. C&EN reporters were in San Diego last week, sharing news stories and photos like this one online. To see more of their coverage, go to acssandiego2016.cenmag.org.
plaques. After zeroing in on atherosclerotic lesions with their targeting ligands, the nanoparticles transport macrophages and cholesterol to the liver for disposal. Dhar hopes to begin clinical trials of the nanoparticles in a few years.—STU BORMAN
HO O
+N
N
NH2
N N
BIOCHEMISTRY
▸ A new twist for ribozyme catalysis
Macrophage-targeting ligand Apolipoprotein-like peptide Magnetic agent
development of synthetic nanoparticles that mimic HDL functionally. In San Diego last week, Dhar and coworkers reported a modified version. The nanoparticles include a sugar-based macrophage-targeting ligand; an apolipoprotein-like peptide to bind cholesterol; and a magnetic agent that allows magnetic resonance imaging of
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C&EN | CEN.ACS.ORG | MARCH 21, 2016
RNAs called ribozymes can catalyze chemical reactions and often play a role in regulating gene expression. Twister ribozymes, which get their name because their overall structure resembles an ancient Egyptian hieroglyph representing twisted flax, are widespread in bacteria and eukaryotes and cut their own phosphodiester backbone. They may accomplish that cleavage through a novel acid catalysis mechanism, according to computational simulations presented at the meeting by Darrin M. York of Rutgers University. Twister ribozymes crystallize in an inactive conformation, which has made it difficult to determine how they selfcleave between adjacent uracil and adenine residues. York and graduate student Colin S. Gaines simulated both the crystalline and solution forms of a twister ribozyme (J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.5b12061). The chemists found that in solution the uracil can adopt an active conformation in
Adenine N NH2 N
O–
N
H O
P
H
N
O–
O
O Guanine
O O
O
N Uracil
HN O
In the proposed mechanism for twister ribozyme self-cleavage (red), a guanine N1 hydrogen-bonds (blue) to the uracil 2’-OH, promoting it as a nucleophile. The protonated adenine N3 hydrogen-bonds to its own 5’-O (green), promoting it as a leaving group. which it stacks with a nearby guanine. The guanine N1 may then hydrogen-bond to the uracil 2’-OH, promoting it as a nucleophile to attack a neighboring phosphate. Meanwhile, the adenine N3 is protonated and can hydrogen-bond to its own 5’-O, promoting it as a leaving group. Although the N1 of adenine residues has been implicated in catalysis by other ribozymes, such a role has not previously been suggested for N3.—
JYLLIAN KEMSLEY
COURTESY OF SHANTA DHAR (NANOPARTICLE); LINDA WANG/C&EN (BOY)
NANOMEDICINES
