NEWS OF THE WEEK
Amphotericin B, with mycosamine in blue and the analog’s eliminated 2'-hydroxyl group in red. OH CO2–
HO
O
HO
+
MEDICINAL CHEMISTRY: Modified
version of amphotericin B will drive search for effective analogs
NH3
O O
A LESS TOXIC ANTIFUNGAL AGENT
OH
OH OH HO
OH OH O O
HO Amphotericin B
HE NATURAL PRODUCT drug amphotericin B is
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a last-resort treatment for life-threatening fungal infections. But it can cause serious side effects, including liver damage, convulsions, and heart failure. Less-toxic versions of amphotericin B have been reported, although none have been approved for use. University of Illinois, Urbana-Champaign, chemistry professor Martin D. Burke and coworkers are trying again. They report a modification that eliminates the drug’s toxicity in human cells, giving hope for a new class of less-toxic derivatives (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja403255s). Amphotericin B is a large cyclic compound with a small appendage called mycosamine. Two years ago, Burke and coworkers showed that mycosamine binding to the fungal sterol ergosterol enables the drug to kill fungi (C&EN, March 21, 2011, page 51). The researchers also believe that mycosamine bind-
BILL GATES FUNDS OPEN SCIENCE SITE OPEN ACCESS: ResearchGate raises
$35 million to mount challenge to traditional science publishing
COMMUNITY Chemists are ResearchGate’s fourth-largest membership group.
A
GROUP OF INVESTORS that includes Micro-
soft founder and philanthropist Bill Gates has invested $35 million in ResearchGate, a fiveyear-old Berlin-based social networking website for scientists. The site, a kind of Facebook for scientists, hopes to upend the traOthera 34% ditional world of peer-reviewed Medicine 21% scholarly publishing. Gates, who is known for his Biology support of scientific endeavors 17% Agricultural to eradicate disease, particularly science Engineering in developing countries, had no 6% 8% Computer comment on the investment. Chemistry science The money will be used to spur 8% 6% innovative ways to share and search b Number of members = 3.5 million for scientific data online, says Ijad Madisch, ResearchGate’s cofounder a Includes physics, math, psychology, and other science professionals. b Includes some individuals and CEO. So far, nearly 3 million users, who registered in more than one discipline. including more than 1.3 million life SOURCE: ResearchGate CEN.ACS.ORG
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ing to cholesterol in patients causes the drug’s side effects. They now find that deleting mycosamine’s 2'-hydroxyl group gives an analog that doesn’t bind cholesterol, retains most of the parent compound’s potency, and in lab studies eliminates side effects in human cells. Natural product specialist Michio Murata of Osaka University calls the reduced toxicity a “surprise.” He says the derivative could be “an important lead compound for developing efficacious and safe antifungal drugs.” Amphotericin B expert Erick Carreira of Swiss Federal Institute of Technology, Zurich, cautions that the paper’s experimental data on cholesterol interactions are subject to interpretations different from those made by Burke’s group. Carreira notes that it remains to be seen whether a derivative “generated through multistep synthetic sequences, as described in the paper, will be sufficient to displace the natural product from the clinic.” Another amphotericin B expert, Maciej Baginski of Gdansk University of Technology, in Poland, says the study’s experiments don’t conclusively establish the 2'-hydroxyl group’s role in sterol binding. But he notes that if the new analog’s lack of toxicity “is confirmed by further studies, including in vivo animal experiments, it will open a new branch of amphotericin B derivatives that may eventually bring a new lead molecule.”—STU BORMAN
scientists and nearly 270,000 chemists, have registered to use the website. Rafael Luque Alvarez de Sotomayor, a professor of organic chemistry at Spain’s University of Cordoba, has used the site since 2008. He calls it “a reliable platform to showcase research and to get in touch with other researchers.” It can aid the careers of young scientists, such as that of a Philippines-based researcher whom Sotomayor says he met through the site. In 2011, they published a paper in Green Chemistry on converting waste oil into biodiesel fuel (DOI: 10.1039/c1gc15908a). But ResearchGate’s goal is to become more than a networking tool. Madisch says he wants to see the website become a publishing platform to replace traditional peer-reviewed journals. Website members can publish both positive and negative results on ResearchGate, says Madisch, who has a Ph.D. in virology from Hannover Medical School, in Germany. Peers can review research publicly instead of behind the scenes and comment more quickly than is now the case, he says. Sotomayor says he is not convinced that ResearchGate can substitute for peer-reviewed journals and sees it more as a networking site. Still, traditional publishers are eyeing ResearchGate and similar websites warily. One scientific publisher, Reed Elsevier, purchased ResearchGate competitor Mendeley in April. Elsevier said the purchase will increase its engagement with researchers.—MARC REISCH
JUNE 17, 2013
