caa a22 4500 445879068 CHVBK 20180317145536.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11030-010-9285-y doi (NATIONALLICENCE)springer-10.1007/s11030-010-9285-y Design, synthesis and activity evaluation of mannose-based DC-SIGN antagonists [Elektronische Daten] [Nataša Obermajer, Sara Sattin, Cinzia Colombo, Michela Bruno, Urban Švajger, Marko Anderluh, Anna Bernardi] 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. Springer Science+Business Media B.V., 2010 Anti-infectives nationallicence Carbohydrates nationallicence DC-SIGN nationallicence Dendritic cell-based assay nationallicence Glycoconjugates nationallicence Glycomimetics nationallicence BSA : Bovine serum albumin nationallicence CFSE : Carboxyfluorescein succinimidyl ester nationallicence CRD : Carbohydrate- recognition domain nationallicence DC : Dendritic cell nationallicence DCC : Dicyclohexyl carbodiimide nationallicence DC-SIGN : Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin nationallicence DMA : N,N-Dimethylacetamide nationallicence DMAP : 4-Dimethylaminopyridine nationallicence DMSO : Dimethyl sulfoxide nationallicence EDC : 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide nationallicence FBS : Fetal bovine serum nationallicence HATU : O-(7-Azabenzotriazole)- N,N,N′,N′ - tetramethyluronium hexafluorophosphate nationallicence LPS : Lipopolysaccharide nationallicence MCPBA : m-Chloroperoxybenzoic acid nationallicence PAMPs : Pathogen-associated molecular patterns nationallicence PBS : Phosphate buffered saline nationallicence PFP : Pentafluorophenyl nationallicence rhGM-CSF : Recombinant human granulocyte-macrophage colony-stimulating factor nationallicence rhIL-4 : Recombinant human interleukin-4 nationallicence RMSD : Root mean square deviation nationallicence SAR : Structure-activity relationship nationallicence SDS : Sodium dodecyl sulfate nationallicence SPR : Surface-plasmon resonance nationallicence THF : Tetrahydrofuran nationallicence TLC : Thin-layer chromatography nationallicence TLR : Toll-like receptor nationallicence ManLAM : Mannosylated lipoarabinomannan nationallicence TMSOTf : Trimethylsilyl triflate nationallicence Obermajer Nataša Department of Biotechnology, Jozef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia aut Sattin Sara Dipartimento di Chimica Organica e Industriale and CISI, Università degli Studi di Milano, via Venezian 21, 20133, Milano, Italy aut Colombo Cinzia Dipartimento di Chimica Organica e Industriale and CISI, Università degli Studi di Milano, via Venezian 21, 20133, Milano, Italy aut Bruno Michela Dipartimento di Chimica Organica e Industriale and CISI, Università degli Studi di Milano, via Venezian 21, 20133, Milano, Italy aut Švajger Urban Blood Transfusion Center of Slovenia, Šlajmerjeva 6, 1000, Ljubljana, Slovenia aut Anderluh Marko Department of Medicinal Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000, Ljubljana, Slovenia aut Bernardi Anna Dipartimento di Chimica Organica e Industriale and CISI, Università degli Studi di Milano, via Venezian 21, 20133, Milano, Italy aut Molecular Diversity Springer Netherlands 15/2(2011-05-01), 347-360 1381-1991 15:2<347 2011 15 11030 https://doi.org/10.1007/s11030-010-9285-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11030-010-9285-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Obermajer Nataša Department of Biotechnology, Jozef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia aut NATIONALLICENCE 700 1- Sattin Sara Dipartimento di Chimica Organica e Industriale and CISI, Università degli Studi di Milano, via Venezian 21, 20133, Milano, Italy aut NATIONALLICENCE 700 1- Colombo Cinzia Dipartimento di Chimica Organica e Industriale and CISI, Università degli Studi di Milano, via Venezian 21, 20133, Milano, Italy aut NATIONALLICENCE 700 1- Bruno Michela Dipartimento di Chimica Organica e Industriale and CISI, Università degli Studi di Milano, via Venezian 21, 20133, Milano, Italy aut NATIONALLICENCE 700 1- Švajger Urban Blood Transfusion Center of Slovenia, Šlajmerjeva 6, 1000, Ljubljana, Slovenia aut NATIONALLICENCE 700 1- Anderluh Marko Department of Medicinal Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000, Ljubljana, Slovenia aut NATIONALLICENCE 700 1- Bernardi Anna Dipartimento di Chimica Organica e Industriale and CISI, Università degli Studi di Milano, via Venezian 21, 20133, Milano, Italy aut NATIONALLICENCE 773 0- Molecular Diversity Springer Netherlands 15/2(2011-05-01), 347-360 1381-1991 15:2<347 2011 15 11030 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer