title: Structural modifications of salicylates: inhibitors of human CD81-receptor HCV-E2 interaction.
abstract: Starting point of the present paper was the result of a virtual screening using the open conformation of the large extracellular loop (LEL) of the CD81-receptor (crystal structure: PDB-ID: 1G8Q). After benzyl salicylate had been experimentally validated to be a moderate inhibitor of the CD81-LEL-HCV-E2 interaction, further optimization was performed and heterocyclic-substituted benzyl salicylate derivatives were synthesized. The compounds were tested for their ability to inhibit the interaction of a fluorescence-labeled antibody to CD81-LEL using HUH7.5 cells. No compound showed an increase concerning the inhibition of the protein-protein interaction compared to benzyl salicylate.
authors.affiliation: Pharmaceutical and Medicinal Chemistry, Saarland University, Saarbrücken, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Holzer
authors.forename: Sigrid
authors.initials: S
authors.lastname: Ziegler
authors.forename: Alexander
authors.initials: A
authors.lastname: Neugebauer
authors.forename: Bernd
authors.initials: B
authors.lastname: Kronenberger
authors.forename: Christian D
authors.initials: CD
authors.lastname: Klein
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D006801:Humans; D011485:Protein Binding; D012459:Salicylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000998:Antiviral Agents; C554798:CD81 protein, human; D012459:Salicylates; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; C039672:benzyl salicylate