+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Selective selenol fluorescent probes: design, synthesis, structural determinants, and biological applications



Selective selenol fluorescent probes: design, synthesis, structural determinants, and biological applications



Journal of the American Chemical Society 137(2): 757-769



Selenium (Se) is an essential micronutrient element, and the biological significance of Se is predominantly dependent on its incorporation as selenocysteine (Sec), the genetically encoded 21st amino acid in protein synthesis, into the active site of selenoproteins, which have broad functions, ranging from redox regulation and anti-inflammation to the production of active thyroid hormones. Compared to its counterpart Cys, there are only limited probes for selective recognition of Sec, and such selectivity is strictly restricted at low pH conditions. We reported herein the design, synthesis, and biological evaluations of a series of potential Sec probes based on the mechanism of nucleophilic aromatic substitution. After the initial screening, the structural determinants for selective recognition of Sec were recapitulated. The follow-up studies identified that probe 19 (Sel-green) responds to Sec and other selenols with more than 100-fold increase of emission in neutral aqueous solution (pH 7.4), while there is no significant interference from the biological thiols, amines, or alcohols. Sel-green was successfully applied to quantify the Sec content in the selenoenzyme thioredoxin reductase and image endogenous Sec in live HepG2 cells. With the aid of Sel-green, we further demonstrated that the cytotoxicity of different selenocompounds is correlated to their ability metabolizing to selenols in cells. To the best of our knowledge, Sel-green is the first selenol probe that works under physiological conditions. The elucidation of the structure-activity relationship for selective recognition of selenols paves the way for further design of novel probes to better understand the pivotal role of Sec as well as selenoproteins in vivo.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 058822116

Download citation: RISBibTeXText

PMID: 25562612

DOI: 10.1021/ja5099676


Related references

Development of Zn(2+) selective fluorescent probes for biological applications. Yakugaku Zasshi 133(10): 1087-1092, 2014

Synthesis and biological applications of two novel fluorescent proteins-labeling probes. Bioorganic & Medicinal Chemistry Letters 19(11): 2957-2959, 2009

Design and synthesis of naltrindole analogues as delta opioid receptor selective fluorescent probes. Abstracts of Papers American Chemical Society 202(1-2): MEDI 155, 1991

Synthesis, spectroscopic properties, and biological applications of eight novel chlorinated fluorescent proteins-labeling probes. Journal of Fluorescence 24(3): 775-786, 2015

Design, synthesis and biological evaluation of naphthalimide-based fluorescent probes for α1-adrenergic receptors. Drug Discoveries & Therapeutics 8(1): 11-17, 2014

Design, synthesis, and biological evaluation of potent discodermolide fluorescent and photoaffinity molecular probes. Organic Letters 7(23): 5199-5202, 2005

Glycolipid-based TLR4 Modulators and Fluorescent Probes: Rational Design, Synthesis, and Biological Properties. Chemical Biology & Drug Design 88(2): 217-229, 2016

Design and synthesis of highly sensitive and selective fluorescein-derived magnesium fluorescent probes and application to intracellular 3D Mg2+ imaging. Journal of the American Chemical Society 126(50): 16353-16360, 2004

Design and synthesis of fluorescent probes for selective detection of highly reactive oxygen species in mitochondria of living cells. Journal of the American Chemical Society 129(34): 10324-5, 2007

New fluorescent 2-phenylindolglyoxylamide derivatives as probes targeting the peripheral-type benzodiazepine receptor: design, synthesis, and biological evaluation. Journal of Medicinal Chemistry 50(2): 404-407, 2007

Fluorescent dendritic nanoprobes: a new class of fluorescent probes for biological applications. Biophysical Journal 104(7): 1394-1394, 2013

Design, synthesis, and biological evaluation of 2-aryl benzothiazoles as potent, selective, brain-permeable amyloid probes. Abstracts of Papers American Chemical Society 225(1-2): MEDI 26, 2003

Design, synthesis and biological evaluation of trimethine cyanine dyes as fluorescent probes for the detection of tau fibrils in Alzheimer's disease brain and olfactory epithelium. Chemmedchem 8(6): 891-897, 2014

Selective homocysteine turn-on fluorescent probes and their bioimaging applications. Chemical Communications 50(53): 6967-6969, 2015

Synthesis and structural/functional characterization of selective M14 metallo-carboxypeptidase inhibitors based on phosphinic pseudo peptide scaffold: Implications on the design of specific optical probes. Journal of Medicinal Chemistry 2019, 2019