TY - JOUR
T1 - Combining cross-coupling reaction and Knoevenagel condensation in the synthesis of glyco-BODIPY probes for DC-SIGN super-resolution bioimaging
AU - Biagiotti, Giacomo
AU - Purić, Edvin
AU - Urbančič, Iztok
AU - Krišelj, Ana
AU - Weiss, Matjaž
AU - Mravljak, Janez
AU - Gellini, Cristina
AU - Lay, Luigi
AU - Chiodo, Fabrizio
AU - Anderluh, Marko
AU - Cicchi, Stefano
AU - Richichi, Barbara
N1 - Funding Information: We thank COST action CA18103 INNOGLY: INNOvation with GLYcans: new frontiers from synthesis to new biological targets. B.R., S.C., C.G. and G.B. thank MIUR-Italy (“Progetto Dipartimenti di Eccellenza 2018-2022” allocated to Department of Chemistry “Ugo Schiff”). We thank Prof. Franck Fieschi and Dr. Corinne Deniaud (Institut de Biologie Structurale in Grenoble, FR) for SPR measurements (data not shown). E.P., J.M., M.W. and M.A. thank the support by ARRS research programme P1-0208. I.U. and A.K. thank the support by ARRS research programme P1-0060. Funding Information: We thank COST action CA18103 INNOGLY: INNOvation with GLYcans: new frontiers from synthesis to new biological targets. B.R. S.C. C.G. and G.B. thank MIUR-Italy (?Progetto Dipartimenti di Eccellenza 2018-2022? allocated to Department of Chemistry ?Ugo Schiff?). We thank Prof. Franck Fieschi and Dr. Corinne Deniaud (Institut de Biologie Structurale in Grenoble, FR) for SPR measurements (data not shown). E.P. J.M. M.W. and M.A. thank the support by ARRS research programme P1-0208. I.U. and A.K. thank the support by ARRS research programme P1-0060. Publisher Copyright: © 2021 Elsevier Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - BODIPY
KW - DC-SIGN
KW - Glycan
KW - Mannose binding lectins
KW - Stimulated emission depletion microscopy
UR - http://www.scopus.com/inward/record.url?scp=85101252688&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.bioorg.2021.104730
DO - https://doi.org/10.1016/j.bioorg.2021.104730
M3 - Article
C2 - 33621778
SN - 0045-2068
VL - 109
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
M1 - 104730
ER -