title: Ab initio conformational space study of model compounds of O-glycosides of serine diamide.
abstract: Relative stabilities of rotamers of the N-acetyl-O-(2-acetamido-2-deoxy-alpha-D-galactopyranosyl)-L-seryl-N'-methyl amide (1) and eleven analogous molecules containing beta-galactose, alpha- and beta-mannose, alpha- and beta-glucose, and L-threonine were calculated to learn whether they could explain the natural preference for 1 in linkages between the carbohydrate and protein in glycoproteins. The lowest energy rotamers of four O-glycoside models of serine diamide were identified with a Monte Carlo search coupled with molecular mechanics (MM2*). These rotamers were further optimized with an ab initio level of theory (HF/6-31G(d)). Subsequently, B3LYP/6-31 + G(d) single point energies were calculated for the most stable HF structures. The most favorable interactions are present in 1 and its glucose analogue. The monosaccharide for the carbohydrate antenna is anchored to the serine residue with an AcNH...O=C-NHMe hydrogen bond in the most stable rotamers. The mannose analogue and the beta-anomers are considerably less stable according to the MM2* and especially to the ab inito energy values. The three analogues have HF/6-31 G(d) energies which are 4-6 kcal mol-1 higher; the single point B3LYP/6-31 + G(d)//HF/6-31 G(d) calculations yield preferences of 3-5 kcal mol-1 for 1. The most stable L-threonine analogues show a behaviour very similarly to the corresponding serine analogues. The ZPE and thermal correction components of the calculated delta H298 and delta G298 values are relatively small (< 0.4 kcal mol-1). However, the T delta S298 term can be as large as 2.6 kcal mol-1. The entropy terms stabilize the alpha-anomers relative to beta-anomers, and ManNAc relative to GalNAc. The largest stabilization effect is observed for one of the rotamers of the alpha-anomer of ManNAc.
authors.affiliation: Department of Inorganic Chemistry, Budapest University of Technology and Economics, 1521 Budapest, Hungary. csonka@web.inc.bme.hu
authors.forename: Gábor I
authors.initials: GI
authors.lastname: Csonka
authors.forename: Gábor A
authors.initials: GA
authors.lastname: Schubert
authors.forename: András
authors.initials: A
authors.lastname: Perczel
authors.forename: Carlos P
authors.initials: CP
authors.lastname: Sosa
authors.forename: Imre G
authors.initials: IG
authors.lastname: Csizmadia
mesh_terms: D003198:Computer Simulation; D003958:Diamide / Q000737:chemistry; D006020:Glycopeptides / Q000737:chemistry; D006027:Glycosides / Q000737:chemistry*; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D015394:Molecular Structure; D012694:Serine / Q000031:analogs & derivatives*; D013816:Thermodynamics; D013912:Threonine / Q000031:analogs & derivatives
chemical_list: D006020:Glycopeptides; D006027:Glycosides; D003958:Diamide; D013912:Threonine; D012694:Serine