Evaluation of the regioselective delactonization of tri-sialic acid lactone by in-solution molecular dynamics simulation

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DOIResolve DOI: http://doi.org/10.1016/j.carres.2012.02.022
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TypeArticle
Journal titleCarbohydrate Research
ISSN0008-6215
Volume354
Pages8793; # of pages: 7
SubjectSialic acid; Lactone; Regioselectivity; Reactant complex; Molecular dynamics
AbstractAn approximate model for the delactonization of tri-sialic acid lactone is presented with two water-layers that led to neutral hydrolysis of δ-lactone. The hydrolytic reactivity was studied with a 10-ns in-solution molecular dynamics simulation. The initial step of this hydrolysis involves a reactant water nucleophile complex via a proton transfer with another water molecule. Therefore, the probability of water molecules localized at the hydrolytic center correlates to the hydrolysis of δ-lactone. The stepwise delactonization of α2,8-(NeuAc)3 lactone results/resulted from water concentration discrepancy near the carbonyl carbon of lactones in two water oxygen⋯carbonyl carbon shells, and the distances of Odouble bondC⋯Owater layers were 2.8 Å and 5.1 Å. Based on in-solution molecular dynamics study, the motion of water molecules over the re-face of the carbonyl groups was used for the quantitative description of the residence probability, p, whose value is 0.11 for lactone I and 0.33 for lactone II. The geometric criteria used to determine the residence statistics are (1) the distance of water–oxygen⋯carbonyl carbon in less than 5.1 Å and (2) the cone angle, θ, of carbonyl Odouble bondC⋯Owater in the range of 85–115°. As expected, a higher residence probability at lactone II led to its faster hydrolysis. Both the radial g(r) and angular p(θ) pair distribution functions of water oxygen and carbonyl groups of lactones ensure a better surrounding hydration encounter for lactone II. In contrast, water molecules around lactone I are deduced due to a steric hindrance by the turn structure of α2,8-(NeuAc)3 lactone.
Publication date
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
IdentifierS0008621512000857
NPARC number21268685
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Record identifier921eb16c-6992-4bbd-9517-debb2c724dfb
Record created2013-11-07
Record modified2016-05-09
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