Effect of protonation of the N-acetyl neuraminic acid residue of sialyl LewisX: A molecular orbital study with insights into its binding properties toward the carbohydrate recognition domain of E-selectin

Fabio Pichierri, Yo Matsuo

研究成果: Article査読

10 被引用数 (Scopus)

抄録

Semiempirical molecular orbital (MO) calculations with an implicit treatment of the water environment were employed in order to assess whether the sialyl LewisX (sLeX) tetrasaccharide binds to E-selectin in the anionic or neutral (i.e., protonated) state. The analysis of the frontier molecular orbitals, electrostatic potential surfaces, and conformational behavior of the sugar indicates that its neutral form possesses the necessary characteristics for binding. In particular, the LUMO level of the neutral sLeX molecule is localized both on the carboxylic group of the N-acetyl neuraminic acid (NeuNAc) residue and on the nearby glycosidic linkage. These two moieties interact with the Arg97 residue of E-selectin, as revealed by a recent crystal structure analysis of the E-selectin/sLeX complex. The energetics of this specific interaction was investigated with the aid of ab initio Hartree-Fock MO calculations, which resulted in a BSSE-corrected binding energy of 16.63 kcal/mol. Our observations could open up new perspectives in the design of sLeX mimics.

本文言語English
ページ(範囲)2751-2757
ページ数7
ジャーナルBioorganic and Medicinal Chemistry
10
8
DOI
出版ステータスPublished - 2002
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

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