The core techniques of structural biology, namely X-ray crystallography and multidimensional NMR, are often not applicable to many important samples due to fundamental experimental problems, such as the lack of suitable crystals in the X-ray case or excessive size or flexibility for NMR. Carbohydrates and glycoproteins are especially challenging in this respect. The novel technique of vibrational ROA (Raman optical activity), which combines the advantages of vibrational spectroscopy with the extra sensitivity to three-dimensional structure of chiroptical methods such as CD (circular dichroism), has much promise for studying a large range of biomolecules, from the smallest to the largest, in aqueous solution. Among other things, it is capable of providing structural information about both the polypeptide and the carbohydrate structure of intact glycoproteins and should become an indispensable spectroscopy tool for glycobiology.

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