NEWS OF THE WEEK
DESIGNER 𝝰-HELIX PEPTIDE CHEMISTRY: γ-Amino acid
stabilizes structural copycat
B A peptide made of α-, β-, and γ- amino acids mimics the shape of an α-helix, with α-amino acids segregated on one side.
a research team has shown that it is possible to create structural mimics of α-helices that are more stable and potentially more useful than the natural versions. Peptide helices are often involved in biological signaling. The work could lead to designed peptides that have desirable properties and are resistant to enzymatic degradation. Chemistry professor Samuel H. Gellman and postdoc Tomohisa Sawada of the University of Wisconsin, Madison, demonstrated the approach by making a 12-amino acid peptide from two β-, two γ-, and eight conventional α-amino acids (J. Am. Chem. Soc., DOI: 10.1021/ja202175a). R
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Y ADDING β- and γ-amino acids to peptides,
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αγααβα
The β- and γ-amino acids of the designed peptide contain cyclic groups that make it more likely to fold. “By incorporating small rings in the backbone, which both β- and γ-amino acids allow us to do, we can build in a level of local folding propensity you can’t get with α-amino acid residues,” Gellman says. In the new peptide, which incorporates two αγααβα repeats, the α-amino acids align on one side of the helix—a feature that could be useful, for example, where only one helix face docks against another structure. Gellman and Sawada show that the α/β/γ peptide is stable enough to form a helix in water and in 50% methanol. “It’s already about as folded as it’s going to get in water,” Gellman says. Water is “the toughest solvent for peptide or protein folding,” he notes. It’s also the solvent that matters in biological settings. Identifying “a helix-forming oligomer that not only contains α-, β-, and γ-amino acids but also forms this structure in aqueous solution is very impressive,” says André Cobb, who studies peptidomimetics α at the University of Reading, England. “The way in which the β and γ units α stack on top of each other within the β helix gives the structure a stability that will be potentially useful in α the design of future peptidomimetα ics.”—CELIA ARNAUD
FLUORO COMPOUNDS MAY DELAY PUBERTY ENVIRONMENT: Children with high blood levels of perfluorochemicals reach puberty later WO PERFLUORINATED CHEMICALS are
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TI M KISER/WI KIPE DIA
linked to a delayed onset of puberty, according to a study of nearly 6,000 children living near a chemical plant (Environ. Sci. Technol., DOI: 10.1021/ es1038694). Since 1951, a DuPont plant near Parkersburg, W.Va., has released perfluorooctanoic acid (PFOA), a surfactant used in Teflon production, into the air and the nearby Ohio River (C&EN, Dec. 19, 2005, page 10). As part of a settlement of a 2001 class-action lawsuit, DuPont agreed to fund research to determine whether PFOA exposure caused measurable health changes in residents near the plant. Scientists had previously shown—in animals only—that PFOA disrupts sexual development. Tony Fletcher, of the London School of Hygiene & Tropical
PFOA from a Teflon manufacturing plant contaminated this portion of the Ohio River and nearby drinking water sources.
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Medicine and a member of the scientific advisory panel established by the settlement, wanted to know whether PFOA also alters sexual development in humans. Fletcher and his colleagues analyzed data gathered as part of the settlement-funded research from 3,076 boys and 2,931 girls between the ages of eight and 18 years. They looked at median blood serum concentrations of PFOA and perfluorooctane sulfonate (PFOS), a related endocrine disrupter that was not produced by the DuPont plant. The children’s PFOA levels were about five times higher than the levels in the general U.S. population, while PFOS levels were only slightly higher than the national average. The researchers then correlated those concentrations with the age at which the children reached puberty. High concentrations of PFOA were associated with delayed puberty in girls only, whereas high levels of PFOS were linked to delays in both boys and girls. For both chemicals, the median delays in puberty were about four to six months—a significant change, but one that’s unlikely to cause health problems, Fletcher says. Christopher Lau, a pharmacologist at the U.S. Environmental Protection Agency, is surprised that PFOS had a stronger association with delayed puberty than PFOA did. Because the children’s PFOS levels were close to average U.S. levels, he thinks that future studies should investigate whether small increases in PFOS exposure can significantly alter development.—LAURA CASSIDAY, special to C&EN
MAY 16, 201 1
