title: Computational design of a sulfoglucuronide derivative fitting into a hydrophobic pocket of dengue virus E protein.
abstract: We performed first-principles calculations based on the ab initio fragment molecular orbital method on dengue virus envelope protein with a hydrophobic ligand, octyl-β-D-glucose to develop an entry inhibitor. As several polar amino acid residues are present at the edge of the pocket, the glucose moiety was chemically modified with hydrophilic groups. Introduction of both sulfated and carboxylated groups on glucose enhanced not only binding affinity to the protein but also inhibition of dengue virus entry. Octyl-2-O-sulfo β-D-glucuronic acid may serve as a molecular probe to study the dengue virus entry process.
authors.affiliation: Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Chemistry, Faculty of Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Sando
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshingai, Kure-shi, Hiroshima 737-0112, Japan.
authors.forename: Fumiteru
authors.initials: F
authors.lastname: Teraoka
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshingai, Kure-shi, Hiroshima 737-0112, Japan.
authors.forename: Tadamune
authors.initials: T
authors.lastname: Otsubo
authors.affiliation: Department of Virology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Morita
authors.affiliation: Department of Chemistry, Faculty of Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tokiwa
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshingai, Kure-shi, Hiroshima 737-0112, Japan. Electronic address: ikeda@ps.hirokoku-u.ac.jp.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan. Electronic address: hidari@jc.u-aizu.ac.jp.
authors.forename: Kazuya I P J
authors.initials: KI
authors.lastname: Hidari
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D005965:Glucuronates / Q000737:chemistry* / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D014775:Virus Activation / Q000187:drug effects / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
chemical_list: D005965:Glucuronates; D014759:Viral Envelope Proteins; C073031:glucuronic acid 3-sulfate; C072281:E protein TH Sman, Dengue virus
keywords: Dengue virus; Entry inhibitor; Envelope protein; Fragment molecular orbital; Glucuronic acid; Sulfation