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Ab Initio Conformational Space Study of Model Compounds of O‐Glycosides of Serine Diamide
Author(s) -
Csonka Gábor I.,
Schubert Gábor A.,
Perczel András,
Sosa Carlos P.,
Csizmadia Imre G.
Publication year - 2002
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20021018)8:20<4718::aid-chem4718>3.0.co;2-s
Subject(s) - conformational isomerism , chemistry , ab initio , ramachandran plot , glycosidic bond , hydrogen bond , molecule , anomeric effect , stereochemistry , amide , ab initio quantum chemistry methods , anomer , computational chemistry , crystallography , protein structure , organic chemistry , enzyme , biochemistry
Abstract Relative stabilities of rotamers of the N‐ acetyl ‐O‐ (2‐acetamido‐2‐deoxy‐ α ‐ D ‐galactopyranosyl) ‐l‐ seryl‐ N′ ‐methyl amide ( 1 ) and eleven analogous molecules containing β ‐galactose, α ‐ and β ‐mannose, α ‐ and β ‐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 ⋅⋅⋅ OC‐NHMe hydrogen bond in the most stable rotamers. The mannose analogue and the β ‐anomers are considerably less stable according to the MM2* and especially to the ab inito energy values. The three analogues have HF/6‐31G(d) energies which are 4–6 kcal mol −1 higher; the single point B3LYP/6‐31+G(d)//HF/6‐31G(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 Δ H 298 and Δ G 298 values are relatively small (<0.4 kcal mol −1 ). However, the T Δ S 298 term can be as large as 2.6 kcal mol −1 . The entropy terms stabilize the α ‐anomers relative to β ‐anomers, and ManNAc relative to GalNAc. The largest stabilization effect is observed for one of the rotamers of the α ‐anomer of ManNAc.