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Conformation of Trisialic Acid Lactone: NMR Spectroscopic Analysis and Molecular Dynamics Simulation
Author(s) -
Chen ChienSheng,
Yu YiPing,
Hsu ChunHua,
Wu YingTa,
Zou Wei,
Fang JimMin,
Wu ShihHsiung
Publication year - 2007
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200700116
Subject(s) - chemistry , lactone , molecular dynamics , stereochemistry , pyranose , steric effects , nuclear magnetic resonance spectroscopy , crystallography , molecular model , cyclohexane conformation , molecule , computational chemistry , hydrogen bond , organic chemistry
The conformation of the trisialic acid lactone α2,8‐(NeuAc) 3 was analyzed by a combination of NMR spectroscopy, molecular modelling and molecular dynamic (MD) calculations. The interresidue NOEs provided 14 important distance restraints for the molecular simulation, and the final simulated structures showed a root mean square deviation of 0.78 for all superimposed structures. Because of the steric hindrance from the spirobicyclic δ‐lactone, the individual sialic acid pyranose rings are considered essential in the chair 5 C 2 conformation. In addition, lactone I close to the nonreducing end adopted a half‐chair A2 HC B9 conformation, whereas lactone II, which is close to the reducing end adopted a skewed twist‐boat C2 S C9 conformation. In the NMR solution structure and in the 1.0‐ns, in‐water MD calculation, the final simulated structures are in the exocyclic torsions (ω7, ω8) = ( gauche – anti ) surface of the energy adiabatic map, where the global minimum can be found. During the in‐water MD simulation, a slight fluctuation in the structure was observed, reflecting the steady conformation of the lactone and the middle residue of the trisaccharide. These data are consistent with a theoretical approach of polysialic acid (PSA) polylactone with torsions (ω7, ω8) = (65°, 175°) and ( Φ , Ψ ) = (75.8°, –112.4°). Thus, we conclude that the PSA polylactone is a right‐hand helix with a rotation angle, μ , of 240° and a repeating unit, n , of 1.5 residues. The structural properties of the PSA lactone discussed within this context differ from the helical epitope of G2 + PSA and may serve in future PSA‐related antigen designs. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)