Dynamics of the Glycosidic Bond: Conformational Space of Lactose

Abstract

The dynamics of the glycosidic bond of lactose was studied by a paramagnetic tagging-based NMR technique, which allowed the collection of an unusually large series of NMR data for a single compound. By the use of distance- and orientation-dependent residual dipolar couplings and pseudocontact shifts, the simultaneous fitting of the probabilities of computed conformations and the orientation of the magnetic susceptibility tensor of a series of lanthanide complexes of lactose show that its glycosidic bond samples syn/syn, anti/syn and syn/anti ϕ/ψ regions of the conformational space in water. The analysis indicates a higher reliability of pseudocontact shift data as compared to residual dipolar couplings with the presently available weakly orienting paramagnetic tagging technique. The method presented herein allows for an improved understanding of the dynamic behaviour of oligosaccharides.

Breaking the Limits in Analyzing Carbohydrate Recognition by NMR Spectroscopy: Resolving Branch‐Selective Interaction of a Tetra‐Antennary N‐Glycan with Lectins

“…These pseudocontact shifts (PCS) depend on the distance between each proton and the metal (proportional to 1/ r 3 ) 6. This methodology has first been applied to the study of small oligosaccharides (di‐, tri‐, and tetrasaccharides),7, 8, 9, 10, 11 then to N ‐glycans. The conformational properties of complex‐type bi‐antennary and high‐mannose‐type N ‐glycans were elucidated and could be resolved in each case down to the level of individual branches 4, 5.…”

“…The measurement of residual dipolar couplings (RDCs) induced by the lanthanide were also attempted to complement the PCS values 16. However, the obtained RDCs were too small to warrant their proper use in the conformational studies.…”

Breaking the Limits in Analyzing Carbohydrate Recognition by NMR Spectroscopy: Resolving Branch‐Selective Interaction of a Tetra‐Antennary N‐Glycan with Lectins

“…[4,5] In its vicinity,acomplexed paramagnetic ion induces significant chemical shift changes of the NMR signals of the glycan as ar esult of dipolar interactions involving the unpaired electron of the metal. These pseudocontact shifts (PCS) depend on the distance between each proton and the metal (proportional to 1/r 3 ).[6] This methodology has first been applied to the study of small oligosaccharides (di-, tri-, and tetrasaccharides), [7][8][9][10][11] then to N-glycans.T he conformational properties of complex-type bi-antennary and high-mannosetype N-glycans were elucidated and could be resolved in each case down to the level of individual branches. [4,5] Proceeding from this experimental basis,weherein extend this concept to the level of high-degree branching,and show that it is possible to experimentally characterize the conformational behavior and recognition properties of ag alactosylated complex-type…”

“…[6] This methodology has first been applied to the study of small oligosaccharides (di-, tri-, and tetrasaccharides), [7][8][9][10][11] then to N-glycans.T he conformational properties of complex-type bi-antennary and high-mannosetype N-glycans were elucidated and could be resolved in each case down to the level of individual branches. [4,5] Proceeding from this experimental basis,weherein extend this concept to the level of high-degree branching,and show that it is possible to experimentally characterize the conformational behavior and recognition properties of ag alactosylated complex-type…”

“…[14,15] Them easurement of residual dipolar couplings (RDCs) induced by the lanthanide were also attempted to complement the PCS values. [16] Scheme 1. Synthesis of the tagged N-glycan 4 and the complexes 4a,b.…”