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Erythropoietin (EPO) is a hormone involved in the production of red blood cells. Synthetic EPO produced via genetically engineered cell cultures is used to treat anemia and—more controversially—to boost athletic performance. EPO is a glycoprotein, and although its protein component is well defined, both natural and synthetic EPO exhibit a wide range of attached oligosaccharides. Wang et al. (see the Perspective by Hsieh-Wilson and Griffin) prepared an EPO sample by a chemical synthesis that maintains a uniform pattern of attached sugars throughout, which may prove helpful in the analysis of how variation in the sugar components of EPO affects function. P. Wang, S. Dong, J.-H. Shieh, E. Peguero, R. Hendrickson, M. A. S. Moore, S. J. Danishefsky, Erythropoietin derived by chemical synthesis. Science 342 , 1357–1360 (2013). [Abstract][Full Text] L. C. Hsieh-Wilson, M. E. Griffin, Improving biologic drugs via total chemical synthesis. Science 342 , 1332–1333 (2013). [Abstract][Full Text]

Vibrational spectroscopy allows for probing the chemistry of enzymatic active sites with a time resolution roughly a millionfold higher than in nuclear magnetic resonance techniques. However, few studies have succeeded in applying vibrational probes to more global structural elucidation, encompassing secondary and tertiary organizational features. Remorino et al. used two-dimensional vibrational echo spectroscopy to uncover the structure of a tertiary contact in the helical dimer of an integrin protein that straddles the cell membrane. The method extracts geometries by measuring distance-dependent rates of vibrational energy transfer between isotopically labeled amino acid residues at specific sites in the peptide sequence. A. Remorino, I. V. Korendovych, Y. Wu, W. F. DeGrado, R. M. Hochstrasser, Residue-specific vibrational echoes yield 3D structures of a transmembrane helix dimer. Science 332 , 1206–1209 (2011). [Abstract][Full Text]