Crystal structure and solution conformation of 1‐N‐acetyl‐β‐D‐glucopyranosyl amine: A model for the glycopeptide linkage

Abstract

SynopsisThe crystal structure of the title compound, a model for the glycosyl linkage between the asparagine side chain and N-acetyl glucosamine in glycoproteins, has been determined and compared to other model structures. The pyranose ring in the crystal is in the 4C1 chair conformation and the amide functions at C1 and at Cz are both oriented such that the amide protons are nearly trans to their respective sugar-ring protons. Coupling constants determined from the fully assigned proton nmr spectrum in aqueous solution are consistent with the conformation in the crystal.

A Synthesis of Heteroaromatic S- and N-β-Glycosides of N-Acetylglucosamine under Phase-Transfer Conditions

“…The bond lengths in the aglycone agree with the published data [29]. Noteworthy is the difference between the ë sp3 -O bonds in the carbohydrate residue (O1-C5 1.441(3) and O1-C1 1.406(4) Å), which has been described for relative compounds (e.g., see [30]) and is a consequence of anomeric effect. Thus, the whole information obtained unequivocally proves the chemical structures of S-β-and N-βglycosides (VI)-(XIII).…”

Glycobiology: Toward Understanding the Function of Sugars

“…While the sugar is not resolved in the crystal structure, the side chain of Asn-34 was well defined. In each of the glycoprotein crystal structures discussed above as well as in those of glycopeptides 31,32 the Asn-GlcNAc linkage displays the same conformation. This conformation has been reported also to be present in solution.…”

“…This conformation has been reported also to be present in solution. 31,33 Given the similarity of the C1sNsCdO atomic sequence of an N-linkage to a CRsNsCdO peptide bond, its preference for planarity and a torsion value of 0°is not surprising. Provided with this observation it is possible to link the dynamic model of the free sugar (each snapshot overlaid on GlcNAc-1) to the side chain of Asn-34 in the crystal structure of RNase B to generate the structure shown in Figure 5.…”

Conformational statistics of the nitrogen linkage in glycopeptides using umbrella sampling

“…NMR [5], circular dichroism [4], and X-ray diffraction [6] were the independent experimental techniques used to determine the conformation of glcNAc-Asn. All three experimental techniques yielded results consistent with trans orientation of the amide N-H bond and the sugar C-H bond for both z~ and zz.…”

“…7/was a threshold energy appropriate for the compound found by performing a preliminary calculation of 20,000 conformations without umbrella weighting on each compound in order to estimate the lowest energy ( or a reasonably close value). The integer portion of the conformational energy was used in equation (6). The value of the weighting rose with each integer step in the conformational energy, but not as last as the energy itself.…”