GOOD CHOLESTEROL COMES INTO FOCUS - C&EN Global

Mar 21, 2011 - HIGH-DENSITY LIPOPROTEIN— the so-called good cholesterol—plays an important role in reducing the risk of heart disease. Yet despite...
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NEWS OF THE WEEK

INSTRUMENTATION: Firms expand

offerings as consolidation trend continues

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burgh Conference on Analytical Chemistry & Applied Spectroscopy (Pittcon) in Atlanta last week said the economic recovery has revived buyer interest. Business conditions, they said, are much stronger than they were a year ago, when the economy was just beginning to improve. Some big instrument makers, including Thermo Fisher Scientific and Agilent, vowed to continue making acquisitions to broaden their product lines. Others, such as Waters and Shimadzu, indicated their intent to remain independent and reliant largely on homegrown advances. “The market is much better today than it was a year ago, when people worried about the fragility of the recovery,” said Michael R. McMullen, president of Agilent’s chemical analysis group. Nick Roelofs, president PETER CUTTS PHOTOGRAPHY

More than 16,000 people attended the Pittcon exhibition and conference.

CIENTIFIC INSTRUMENT makers at the Pitts-

GOOD CHOLESTEROL COMES INTO FOCUS HEART DISEASE: Cross-linking mass

spectrometry gives clues to native structure of high-density lipoprotein

H A model shows how four ApoA-1 chains might organize themselves in HDL.

IGH-DENSITY LIPOPROTEIN—the so-called

good cholesterol—plays an important role in reducing the risk of heart disease. Yet despite its importance, all structural information has come from synthetic HDL particles. Now, biochemists at the University of Cincinnati have obtained the first structural information on HDL isolated from human plasma (Nat. Struct. Mol. Biol., DOI: 10.1038/nsmb.2028). An understanding of HDL’s structural organization “will be highly significant for future development of drugs affecting the antiinflammatory, antioxidant, and antiatherogenic functions of HDL that could lead to new approaches to preventing and reversing coronary heart disease,” says Jere P. Segrest, a researcher studying lipoprotein structure at the University of Alabama, Birmingham. HDL particles aren’t suited to high-resoluWWW.CEN-ONLINE.ORG

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of Agilent’s life sciences group, added that acquisitions will remain part of the firm’s growth strategy. He pointed to the 2010 acquisition of Varian, which brought nuclear magnetic resonance instruments to the firm’s product line, and to this month’s Biocius and Lab 901 purchases, which expanded Agilent’s high-throughput spectroscopy and electrophoresis offerings. Thermo Fisher Scientific CEO Marc N. Casper noted that his firm is “investing to increase the depth of our capabilities.” He cited recent acquisitions, such as reagent supplier Finnzymes and handheld detector maker Ahura Scientific, and noted that the planned $2.1 billion acquisition of ion chromatography expert Dionex should close in the second quarter. Thermo Fisher is waiting for European regulators to clear the purchase. Chromatography leader Waters said technology advances are more important than acquisitions. The firm’s last major acquisition was the 2009 purchase of supercritical fluid chromatography specialist Thar Instruments. Waters used Pittcon this year to showcase the first Thar instrument—a sub-2-µm-particle ultraperformance chromatograph—to be sold under the Waters name. Instrument makers Agilent and Shimadzu said their Japanese employees are safe and facilities are intact after the earthquake and tsunami. But Japanese instrument maker Jeol suffered some damage to its factories in the north of the country, said J. Douglas Meinhart, analytical instruments vice president.—MARC REISCH

tion methods such as X-ray crystallography or NMR. W. Sean Davidson and coworkers instead turned to mass spectrometric analysis of cross-links between lysines to obtain distance constraints they could use to model the most abundant protein in HDL particles, apolipoprotein A-1 (ApoA-1). Synthetic HDL particles—which are built in the lab from HDL’s protein parts—typically contain only three ApoA-1 chains, but the HDL particles that Davidson and coworkers isolated were larger, containing four or five chains. The cross-linking patterns, which are similar regardless of the number of protein chains, suggest that ApoA-1 adopts a symmetric cagelike structure. Size differences among particles with the same number of chains appear to be due to protein chains twisting while maintaining the same contacts. “Surprisingly and importantly, the chemical crosslinking and mass spectrometry results show that ApoA-1 maintains distinct intermolecular contacts regardless of HDL particle size and shape,” says Michael C. Phillips, an HDL researcher at Children’s Hospital of Philadelphia. Even such low-resolution structures could help scientists figure out good places to mutate on the protein to determine how it functions, Davidson says. “That’s going to take us a long way toward understanding how HDL is protective against cardiovascular disease and will help take us to the next step of designing ways to mimic it.”—CELIA ARNAUD

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SEAN DAVIDSON

UPBEAT OUTLOOK AT PITTCON