title: BODIPY-Based Fluorescent Probes for Sensing Protein Surface-Hydrophobicity.
abstract: Mapping surface hydrophobic interactions in proteins is key to understanding molecular recognition, biological functions, and is central to many protein misfolding diseases. Herein, we report synthesis and application of new BODIPY-based hydrophobic sensors (HPsensors) that are stable and highly fluorescent for pH values ranging from 7.0 to 9.0. Surface hydrophobic measurements of proteins (BSA, apomyoglobin, and myoglobin) by these HPsensors display much stronger signal compared to 8-anilino-1-naphthalene sulfonic acid (ANS), a commonly used hydrophobic probe; HPsensors show a 10- to 60-fold increase in signal strength for the BSA protein with affinity in the nanomolar range. This suggests that these HPsensors can be used as a sensitive indicator of protein surface hydrophobicity. A first principle approach is used to identify the molecular level mechanism for the substantial increase in the fluorescence signal strength. Our results show that conformational change and increased molecular rigidity of the dye due to its hydrophobic interaction with protein lead to fluorescence enhancement.
authors.affiliation: Department of Chemistry, Michigan Technological University, Houghton, MI 49931, USA.
authors.forename: Nethaniah
authors.initials: N
authors.lastname: Dorh
authors.affiliation: Department of Chemistry, Michigan Technological University, Houghton, MI 49931, USA.
authors.forename: Shilei
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Physics, Michigan Technological University, Houghton, MI 49931, USA.
authors.forename: Kamal B
authors.initials: KB
authors.lastname: Dhungana
authors.affiliation: Department of Physics, Michigan Technological University, Houghton, MI 49931, USA.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Pati
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei, Taiwan 11529, Republic of China.
authors.forename: Fen-Tair
authors.initials: FT
authors.lastname: Luo
authors.affiliation: Department of Chemistry, Michigan Technological University, Houghton, MI 49931, USA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Michigan Technological University, Houghton, MI 49931, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Tiwari
mesh_terms: D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D000818:Animals; D001059:Apoproteins / Q000737:chemistry* / Q000378:metabolism; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D009211:Myoglobin / Q000737:chemistry* / Q000378:metabolism; D063347:Native Polyacrylamide Gel Electrophoresis; D011485:Protein Binding; D011789:Quantum Theory; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; C515594:8-anilino-1-naphthalenesulfonic acid; D000817:Anilino Naphthalenesulfonates; D001059:Apoproteins; D001896:Boron Compounds; D005456:Fluorescent Dyes; D009211:Myoglobin; C010857:apomyoglobin; D012710:Serum Albumin, Bovine