A near-infrared "turn-on" fluorescent probe with a self-immolative linker for the in vivo quantitative detection and imaging of hydrogen sulfide.
Hydrogen sulfide is a critical biological messenger, but few biologically compatible methods are available for its detection in vivo. Here, we describe the design and synthesis of a novel azide-functionalized near-infrared probe, NIR-Az, for a hydrogen sulfide assay in which a self-immolative linker is incorporated between the azide moiety and phenolic dihydroxanthene fluorophore from a cyanine dye. A large "turn-on" near-infrared fluorescence signal results from the reduction of the azide group of the fluorogenic moiety to an amine, in which the self-immolative linker also enhances the accessibility of NIR-Az to hydrogen sulfide. NIR-Az can select hydrogen sulfide from among 16 analytes, including cysteine, glutathione, and homocysteine. By exploiting the superior properties of NIR-Az, such as its good biocompatibility and rapid cell internalization, we successfully demonstrated its usefulness in monitoring both the concentration- and time-dependent variations of hydrogen sulfide in living cells and animals (detection limit less than 0.26μM), thereby providing a powerful approach for probing hydrogen sulfide chemistry in biological systems.
Hazards Monitoring Bionano Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, South Korea; Department of Polymer Engineering, Graduate School, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, South Korea.
Chul Soon
CS
Park
Hazards Monitoring Bionano Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, South Korea; Nanobiotechnology and Bioinformatics (Major), University of Science & Technology (UST), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, South Korea.
Tai Hwan
TH
Ha
Hazards Monitoring Bionano Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, South Korea; Nanobiotechnology and Bioinformatics (Major), University of Science & Technology (UST), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, South Korea.
Seon-Ae
SA
Choi
Department of Polymer Engineering, Graduate School, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, South Korea.
Duong Nguyen
DN
Nguyen
Department of Polymer Engineering, Graduate School, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, South Korea.
Seonmyeong
S
Noh
Hazards Monitoring Bionano Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, South Korea. Electronic address: oskwon7799@gmail.com.
Oh Seok
OS
Kwon
Hazards Monitoring Bionano Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, South Korea; Nanobiotechnology and Bioinformatics (Major), University of Science & Technology (UST), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, South Korea. Electronic address: cslee@kribb.re.kr.
Chang-Soo
CS
Lee
Department of Polymer Engineering, Graduate School, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, South Korea; School of Polymer Science and Engineering, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, South Korea. Electronic address: hyoon@chonnam.ac.kr.
Hyeonseok
H
Yoon
D000818:Animals; D001386:Azides / Q000737:chemistry; D015374:Biosensing Techniques; D003545:Cysteine / Q000737:chemistry / Q000302:isolation & purification; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry / Q000302:isolation & purification; D006862:Hydrogen Sulfide / Q000737:chemistry / Q000302:isolation & purification*; D013050:Spectrometry, Fluorescence
D001386:Azides; D005456:Fluorescent Dyes; D005978:Glutathione; D003545:Cysteine; D006862:Hydrogen Sulfide
Fluorescence; Hydrogen sulfide; In vivo; Self-immolation; Sensing