title: Design, synthesis and activity evaluation of mannose-based DC-SIGN antagonists.
abstract: In this article, we describe the design, synthesis and activity evaluation of glycomimetic DC-SIGN antagonists, that use a mannose residue to anchor to the protein carbohydrate recognition domain (CRD). The molecules were designed from the structure of the known pseudo-mannobioside antagonist 1, by including additional hydrophobic groups, which were expected to engage lipophilic areas of DC-SIGN CRD. The results demonstrate that the synthesized compounds potently inhibit DC-SIGN-mediated adhesion to mannan coated plates. Additionally, in silico docking studies were performed to rationalize the results and to suggest further optimization.
authors.affiliation: Department of Biotechnology, Jozef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Obermajer
authors.forename: Sara
authors.initials: S
authors.lastname: Sattin
authors.forename: Cinzia
authors.initials: C
authors.lastname: Colombo
authors.forename: Michela
authors.initials: M
authors.lastname: Bruno
authors.forename: Urban
authors.initials: U
authors.lastname: Svajger
authors.forename: Marko
authors.initials: M
authors.lastname: Anderluh
authors.forename: Anna
authors.initials: A
authors.lastname: Bernardi
mesh_terms: D001681:Biological Assay; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors*; D015195:Drug Design; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors*; D008358:Mannose / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding / Q000502:physiology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008358:Mannose; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin