Note The conformational behaviour of the C-glycosyl analogue of sulfatide studied by NMR in SDS micelles Jose ´ Juan Herna ´ndez-Gay, a Luigi Panza, b Fiamma Ronchetti, c F. Javier Can ˜ ada, a Federica Compostella c, * and Jesu ´s Jime ´nez-Barbero a, * a Departamento de Ciencia de Proteı ´nas, Centro de Investigaciones Biolo ´ gicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain b Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Universita ` del Piemonte Orientale, Via Bovio 6, 28100-Novara, Italy c Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Universita ` di Milano, Via Saldini 50, 20133-Milano, Italy Received 9 March 2007; received in revised form 16 April 2007; accepted 22 April 2007 Available online 1 May 2007 Abstract—The conformational behaviour of sulfatide and its C-glycosyl analogue has been studied by using a combination of J and NOE data assisted by molecular mechanics calculations. There is a major exoanomeric conformation around the phi angle of both molecules with two or three conformers contributing to the equilibrium around psi. The MM MM3 * calculations only provide a qualita- tive description of the actual population distribution. Despite this geometrical similarity, the quantitative analysis of the NOE inten- sities at a variety of mixing times indicates that the motion around the pseudoglycosidic linkages of the C-glycosyl analogue is faster than that for the natural compound. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: C-glycosides; Sulfatide; Micelles; NMR; Glycomimetics Sulfatide is a mammalian sulfoglycolipid, which is a mixture of 3-O-sulfo-galactosylceramides containing fatty acid residues of different structure and chain length. The nervonoyl derivative is 1a. Sulfatide is a major component of both the central and peripheral nervous systems, and is also present in subpopulations of neurons and astrocytes, which are nonmyelin-forming cells of the brain. This natural cellular lipid in myelin is localized to the plasma membrane, and functions as a structural component, while in neuron and astrocytes it is located in the intracellular compartment with func- tions not yet well understood. 1 It accumulates in these cells in arylsulfatase A (ASA)-deficient mice, which are a model for the human neurodegenerative disease meta- chromatic leukodystrophy. 2 Distinct sulfatide molecular species may have different distributions. For example, analysis in mice of the molecular species of sulfatide in cultured astrocytes and neurons showed that they con- tain mostly short-chain fatty acid sulfatide with an emphasis for stearic acid, while long-chain (C22–C26) fatty acids are found on sulfatide in myelin. The fatty acid chain length of sulfatide might determine its subcel- lular localization and thereby its function. 1 Further- more, pancreatic islets are demonstrated to contain sulfatide and to exhibit a profile of species different from that of brain. 3 Sulfatide is involved in immunological phenomena. In fact, in the context of the stimulation of T-cells mediated by CD1 proteins, sulfatide binds to all human CD1 mole- cules and also to mouse CD1d. 4 Treatment of wild-type (but not CD1d-deficient) mice with sulfatide prevented the development of experimental allergic encephalomy- elitis (EAE). 5 Furthermore, antibodies to sulfatide occur in sera of some patients with demyelinating neuropa- thies and with newly diagnosed insulin-dependent diabe- tes mellitus caused by immunological destruction of insulin-secreting pancreatic islet b-cells. 6,7 0008-6215/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.carres.2007.04.023 * Corresponding authors. E-mail addresses: federica.compostella@ unimi.it; jjbarbero@cib.csic.es Carbohydrate Research 342 (2007) 1966–1973