Combining cross-coupling reaction and Knoevenagel condensation in the synthesis of glyco-BODIPY probes for DC-SIGN super-resolution bioimaging

Giacomo Biagiotti; Edvin Purić; Iztok Urbančič; Ana Krišelj; Matjaž Weiss; Janez Mravljak; Cristina Gellini; Luigi Lay; Fabrizio Chiodo; Marko Anderluh; Stefano Cicchi; Barbara Richichi

doi:10.1016/j.bioorg.2021.104730

Combining cross-coupling reaction and Knoevenagel condensation in the synthesis of glyco-BODIPY probes for DC-SIGN super-resolution bioimaging

Bioorg Chem. 2021 Apr:109:104730. doi: 10.1016/j.bioorg.2021.104730. Epub 2021 Feb 16.

Authors

Affiliations

¹ Department of Chemistry 'Ugo Schiff', University of Firenze, Via della Lastruccia 3/13, 50019 Sesto Fiorentino FI, Italy.
² University of Ljubljana, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
³ Laboratory of Biophysics, Condensed Matter Physics, Department Jožef Stefan Institute, Jamova cesta 39, SI-1000 Ljubljana, Slovenia.
⁴ Department of Chemistry and CRC Materiali Polimerici (LaMPo), University of Milan, via Golgi 19, 20133 Milan, Italy.
⁵ Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, Netherlands; Institute of Biomolecular Chemistry (ICB), Italian National Research Council (CNR), Pozzuoli, NA, Italy.
⁶ University of Ljubljana, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Aškerčeva 7, SI-1000 Ljubljana, Slovenia. Electronic address: Marko.Anderluh@ffa.uni-lj.si.
⁷ Department of Chemistry 'Ugo Schiff', University of Firenze, Via della Lastruccia 3/13, 50019 Sesto Fiorentino FI, Italy. Electronic address: stefano.cicchi@unifi.it.
⁸ Department of Chemistry 'Ugo Schiff', University of Firenze, Via della Lastruccia 3/13, 50019 Sesto Fiorentino FI, Italy. Electronic address: barbara.richichi@unifi.it.

PMID: 33621778
DOI: 10.1016/j.bioorg.2021.104730

Abstract

Lectins are involved in a wide range of carbohydrate mediated recognition processes. Therefore, the availability of highly performant fluorescent tools tailored for lectin targeting and able to efficiently track events related to such key targets is in high demand. We report here on the synthesis of the glyco-BODIPYs 1 and 2, based on the efficient combination of a Heck-like cross coupling and a Knoevenagel condensation, which revealed efficient in addressing lectins. In particular, glyco-BODIPY 1 has two glycosidase stable C-mannose residues, which act as DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) targeting modules. By using live-cell fluorescence microscopy, we proved that BODIPY-mannose 1 was efficiently taken up by immune cells expressing DC-SIGN receptors. Super-resolution stimulated emission depletion (STED) microscopy further revealed that the internalized 1 localized in membranes of endosomes, proving that 1 is a reliable tool also in STED applications. Of note, glyco-BODIPY 1 contains an aryl-azido group, which allows further functionalization of the glycoprobe with bioactive molecules, thus paving the way for the use of 1 for tracking lectin-mediated cell internalization in diverse biological settings.

Keywords: BODIPY; DC-SIGN; Glycan; Mannose binding lectins; Stimulated emission depletion microscopy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Boron Compounds / chemical synthesis
Boron Compounds / chemistry*
Cell Adhesion Molecules / analysis*
Cell Line
Dose-Response Relationship, Drug
Glucose / chemistry
Healthy Volunteers
Humans
Lectins, C-Type / analysis*
Mannose / chemistry
Molecular Structure
Receptors, Cell Surface / analysis*
Structure-Activity Relationship

Substances

4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
Boron Compounds
Cell Adhesion Molecules
DC-specific ICAM-3 grabbing nonintegrin
Lectins, C-Type
Receptors, Cell Surface
Glucose
Mannose