Conformational analysis of the sialylα(2→3/6)N‐acetyllactosamine structural element occurring in glycoproteins, by two‐dimensional NOE 1H‐NMR spectroscopy in combination with energy calculations by hard‐sphere exo‐anomeric and molecular mechanics force‐field with hydrogen‐bonding potential

Open Access
Publisher Website
Google Scholar
Abstract
The conformation is described of the sialylα(2 → 3/6)N-acetyllactosamine structural element, frequently occurring in glycoproteins. NOE spectroscopy of NeuAcα(2 → 3) Galβ(1 → 4)GlcNAcβ(1 → N)Asn and NeuAcα-(2 → 6)Galβ(1 → 4)GlcNAcβ(1 → N)Asn is presented and for each glycosidic linkage, except for the α(2→6)-linkage, a number of interglycosidic NOEs are measured. The analysis of these effects is performed using a full relaxation matrix. Analysis of intraresidue NOEs provides a calibration of the calculation method. Hard-sphere exo-anomeric (HSEA) energy calculations indicate a single conformation for the β(1 → 4)-linkage in both compounds, both being consistent with the NOE data. HSEA and molecular-mechanics force-field with hydrogen-bonding potential energy calculations both indicate the existence of three preferred conformations for the α(2 → 3)-linkage. The analysis of the NOE spectra are consistent with a distribution over two or three of these conformations; by combination with the energy diagram for this linkage the existence of onyl a single conformation can be excluded. The NOE spectrum of the compound with the α(2 → 6)-linkage indicates a gt orientation for the Gal C-6 hydroxymethyl group. On this basis, the HSEA energy calculations for the α(2→6)-linkage indicate an extended low-energy surface with a number of preferred conformations. The absence of NOEs across this linkage is interpreted in terms of a non-rigid, but overall folded conformation of the NeuAcα(2 → 6)Galβ(1 → 4)GlcNAcβ structural element. This provides an explanation for the shift effects induced by α(2 → 6) attachment of NeuAc to the N-acetyllactosamine unit.

This publication has 36 references indexed in Scilit: