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11Th International Symposium on Glycoconjugates/ June 30 – Glycoconjugate Journal (1991) 8:125-278 11th International Symposium on Glycoconjugates/ 11 e Symposium international sur les glycoconjugu s, June/Juin 30 - July/Juillet 5 1991 S1. OLIGOSACCHARIDE CONFORMATION/CONFORMATION DES OLIGOSACCHARIDES 1.1 hydrate sheet in BGSG molecules shows an unique situation, when the NMR SPECTROSCOPIC STUDIES ON GLYCOPROTEINS carbohydrate-carbohydrate inter-actions, first of all, determine the spatial architecture of the molecules. The proposed structure are corres- J.F.G. Vliegenthart; K. Hfird and J.P. Kamerling. ponded to experimental (aquametric) data. Bijvoet Center, Department of Bio-Organic Chemistry, Utrecht Univer- sity, Utrecht, The Netherlands. During the last decade NMR spectroscopy has been successfully used to determine the primary structure of the carbohydrate chains of numerous glycoproteins. Due to the complexity of most glycoproteins, manifested 1.3 in several N- and/or O-glycosylation sites combined with microhetero- TEMPERATURE DEPENDENT TIME-RESOLVED geneity, it is usually necessary to conduct aH-NMR studies on isolated FLUORESCENCE ENERGY TRANSFER REVEALS ENERGY free oligosaccharides. However, NMR spectroscopy is also the sole BARRIERS IN THE FLEXIBILITY OF TWO OF THE method by which the solution structure of an intact glycoprotein can be derived. Attempts are now being made to use different NMR spectro- ANTENNA OF A TRIANTENNARY GLYCOPEPTIDE scopic techniques for this purpose: Kevin G. Rice, Pengguang Wu, Ludwig Brand, and Yuan C. Laser photo-CIDNP studies have been performed on both an intact Lee. glyeoprotein and on its enzymatically deglycosylated form, thereby Department of Biology, Johns Hopkins University, Baltimore, Maryland giving information on the effect of the carbohydrate chain on the USA conformation of the protein. We have prepared three isomers of a triantennary glycopeptide (shown In order to observe sequential NOE-contacts in a protein, NMR below) which have a fluorescence donor (naphthyl-2-acetyl) attached to experiments have to be carried out in 1H20. For glycoproteins this the N-terminus of the peptide and differ in the location of a fluorescence implies that also carbohydrate amide protons are observed. Therefore, acceptor (dansyl) which is attached to one of the terminal Gal residues 2D NMR experiments have been conducted in aqueous solution on (either 6' 8, or 6). Fluorescence energy transfer measurements using the several differently branched glycoprotein glycans, including diantennary F6rster equation provided an average distance separating the donor from chains with and without intersecting GlcNAc, and tetrasialo tetraanten- the acceptor in each triantennary isomer. Time-resolved fluorescence nary oligosaccharides. Furthermore, the use of 3D NMR in ~H20 for energy transfer measurements revealed two populations of conformers structural studies on highly branched N-glycans will be illustrated. for Gal 6 or 6' isomers. One conformer contained the antenna folded back towards the core region, and a second was in an extended conformation. The antenna containing the acceptor attached to Gal 8 was found to be only in the extended conformation. 1.2 i Gfl1-4GNU1-2Mna l -.6 Ala-NH-Donor PRINCIPLES OF SPATIAL ORGANIZATION OF 6' ~ / O-GLYCOSYLPROTEINS Mn p l -.4GNp1-4GN#-Asn A.Ya.Avanov. Aeceptor 8 / G~ I -,4GNfll ~4Mnal ~3 G.'Gal Institute of Biochemistry, Yerevan, Armenia, USSR 6 / GN..GlcNAc At first on example of blood-group-specific glycoproteins (BGSG) by G~ I --4GNp1-2 Mn..Man method of theoretical conformational analysis the general principles of spatial construction of O-glycosylated glycoproteins are concluded. We have now determined the ratio of extended and folded conformers These centauric macromolecules are characterised by high contention of at temperatures varied from 0°C to 40°C. At 0°C the folded conformation carbohydrate component substituting side chains, practically, all of dominated in both the Gal 6 and 6' isomers. Increasing the temperature hydroxyaminoacide residues (Thr Ser). Calculation with consideration systematically shifted the equilibrium until at 40°C, the extended con- of nonbonded interaction shows, that the carbohydrat-carbohydrate former predominated. The Gal 6 and 6' isomer each showed different (side-side) and short range carbohydrate-peptide (side-backbone) sensitivity to the temperature dependent conformational change, while interactions are the dominant factors in spatial organization of this class the Gal 8 isomer remained only in the extended form within the glycoproteins. temperature range tested. These data allowed calculation of AH and For BGSG concretely we proposed "tunnel" structure (0 = 50A,, AS for the conformational change. Both the Gal 6 and 6' isomer showed L = 300A), in which the polypeptide backbone is covered with layer of a positive AS for unfolding, however the entropy change for the Gal 6' closely packed carbohydrate chains. The presence of compact carbo- isomer was twice that of Gal 6. 126 Oligosaccharide conformation 1.4 has been studied by functional group replacement. Here we deal with FAVOURED CONFORMATIONS AND ORIENTATIONS OF aspects of this work that involve synthesis of various amino derivatives THE SACCHARIDE CHAIN OF GLYCOSPHINGO-LIPIDS AT of epitope 1. THE MEMBRANE SURFACE: X-RAY ANALYSES AND The strategy to obtain different N-acyl derivatives employed a key THEORETICAL CALCULATIONS acceptor molecule protected by a N-carbobenzoxy group (Cbz). Glyco- sylations used a thioglycoside which was activated by in situ generation Per-Georg Nyholm. of iodonium ions 2. Under these conditions the disaccharides 2 and 3 were Dept. Medical Biochemistry, University of GOteborg, Box 33031, prepared in excellent yields. Regioselective protection of 2 followed by S-40033 G6teborg, Sweden. glycosylation gave the trisaccharide 4. The derivatives 5, 6 and 7 were In glycosphingolipids (GSL) the conformation at the saccharide- then obtained, in two steps, respectively from 2, 3 and 4. Upon ceramide linkage is crucial for the orientation of the saccharide chain at hydrogenolysis, the N-carbobenzoxy derivatives 5 and 7 gave 8 and 9. the membrane surface. As a complement to our x-ray single crystal These derivatives were either isolated as their hydrochloride salt, or investigations (1,2) theoretical calculations have been performed in subsequently treated with various acylating agents to yield the deriva- order to define preferred conformations and possible orientations of the tives 10-13. saccharide chain. The calculations (3) indicate that, especially for bulky These analogues were used in competitive binding studies to deter- and curved saccharide chains, there is a limited range of admissible mine the importance of the N-acetyl group to the interaction between saccharide chain orientations. the antigen and the combining site of the antibody SYA/J6. The In the present study molecular mechanics calculations were applied on conformation of these oligosaccharides was determined by nmr and various monoglycosylceramides in order to obtain detailed information potential energy calculation methods and the results obtained are being about the conformational energetics of the saccharide-ceramide linkage. used to elaborate a molecular graphics based model of the antigen- Relaxed potential energy maps (+,+,0) and complete energy minimiza- antibody complex. tions show a limited number of favoured conformations (4) which are compatible with x-ray and NMR data. According to these calculations OR e 0 OMe intramolecular hydrogen bonds and dipole-dipole interactions play an important role in stabilizing certain conformations of the saccharide- ceramide linkage. Moreover, the admissible range of saccharide chain ReoD~~HNRX orientations is further restricted if steric interference of the saccharide 2 R 1 = Cbzl R E = )CHPh I R3 = I:lc chain with the membrane surface is accounted for (3,4). RO 0 RO 3 R I = COCF3I R e = )CHPhl R s = FIc The accumulated information on the conformation of the saccharide- 5 R 1 = Cbz; R e, R 3 = H ceramide linkage was applied to model the orientation of the oligosac- 6 R z = COCFg; R E , R '~ = H charide chains of different globo GSL with binding epitopes for E. coil B Rlw Raw R 3 -- H G-adhesins. The calculations (5) indicate that for GSL in a membrane 10 R 1 = COELI R E , R 3 = H layer certain epitopes are efficiently exposed whereas others are inacces- 11 R 1 = COtBu; R e , R 3 = H sible. This provides an explanation of crypticity phenomena which have been observed for epitopes on globo GSL (5,6,7). DR e 0 Orle 1) Nyholm, P.G., Sundell, S. & Pascher, I. (1990). Chem. Phys. Lipids. 52, 1-10. Reo~~HNR x 2) Pascher, I., Lundmark, M., Nyholm, P.G. & Sundell, S. (1991) Biochim. biophys. Acta, submitted. R30~-/~.-D'~ 1 R 1 = Rci R e , R s = H 3) Nyholm, P.G., Samuelsson, B.E., Breimer, M. & Pascher, I. (1989) H3C~ I~ ~nn3 4 Rt = P-BZl R e = )CHPh| R3 = fie J. Molec. recognition 2, 103-113. '/~'0~ OR 7 R 1 = Cbzl R e , R 3 = H 4) Nyholm P.G., (1991) to be submitted. RO 9 RX: Re: R~ = H 5) Str6mberg, N., Nyholm, P.G., Pascher, I., Normark, S. (1991), OR 3 12 R 1 -- COtB"; REp R 3 = H submitted_ 6) Head, S. Ramotar, K., & Lingwood, C. (1990) Infection and 13 R 1 = COCr3| R2w R 3 = H immunity 58, 1532-37. 7) Lampio, A., Siissalo, I., Gahmberg, C. (1988) Eur. J. Biochem. 178, 1_ N.I.A Carlin, A.A Lindberg, K. Bock, and D.R. Bundle, Carbo- 87-91. hydr. Res.56(1977) 363; 2. P. Konradsson, D.R. Mootoo, R.E. McDevitt, and B. Fraser-Reid, J. Chem. Soc., Chem, Commun., (1990) 270. 1.5 1.6 SYNTHESIS OF MODIFIED DI- AND TRI-SACCHARIDE N.M.R. AND CONFORMATIONAL ANALYSIS OF ANALOGUES OF THE SHIGELLA FLEXNERI VARIANT DERIVATIVES OF a-2,8-SIALYL OLIGOSACCHARIDES O-ANTIGEN POLYSACCHARIDE AND COMPARISON WITH THE NATIVE COMPOUNDS F.I. Auzanneau, and D.R. Bundle. Herbert Baumann, Jean-Robert Brisson, Francis Michon and Institute for Biological Sciences, National Research Council of Canada, Harold J. Jennings. Ottawa, Ontario, Canada, KIA 0R6.
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