title: Synthesis of a BODIPY library and its application to the development of live cell glucagon imaging probe.
abstract: The first BODIPY library (BD) was synthesized, and a highly selective glucagon sensor, Glucagon Yellow (BD-105), was discovered by fluorescence image-based screening method. BD library was synthesized via a Knoevenagel-type condensation reaction with 160 benzaldehydes and the 1,3 dimethyl-BODIPY scaffold. Using BD compounds, a fluorescence image-based screening was performed against three cell lines including AlphaTC1 and BetaTC6 cells which secret glucagon and insulin, respectively, and HeLa as control cells. Out of the 160 candidate probes, one compound, Glucagon Yellow, exhibited selective staining only in AlphaTC1 cells. The selectivity of Glucagon Yellow toward glucagon was confirmed in vitro by comparison of its fluorescence intensity change against 19 biologically relevant analytes. Subsequent immunostaining experiments revealed that Glucagon Yellow and the glucagon antibody colocalized in pancreas tissue, showing a high quantitative correlation analysis by the Pearson's coefficient constant (R(r) = 0.950). These results demonstrated the potential application of Glucagon Yellow as a glucagon imaging agent in live cells and tissues.
authors.affiliation: Department of Chemistry, New York University, New York, New York 10003, USA.
authors.forename: Jun-Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Nam-young
authors.initials: NY
authors.lastname: Kang
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Kim
authors.forename: Animesh
authors.initials: A
authors.lastname: Samanta
authors.forename: Suihan
authors.initials: S
authors.lastname: Feng
authors.forename: Hyeong Kyu
authors.initials: HK
authors.lastname: Kim
authors.forename: Marc
authors.initials: M
authors.lastname: Vendrell
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Park
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Chang
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D001896:Boron Compounds / Q000032:analysis* / Q000138:chemical synthesis* / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival; D005456:Fluorescent Dyes / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry; D005934:Glucagon / Q000031:analogs & derivatives / Q000032:analysis* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D015394:Molecular Structure; D011789:Quantum Theory; D054852:Small Molecule Libraries
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D005456:Fluorescent Dyes; D054852:Small Molecule Libraries; C544198:glucagon yellow; D005934:Glucagon