TY - JOUR
T1 - An environmentally sensitive molecular rotor as a NIR fluorescent probe for the detection of islet amyloid polypeptide
AU - Lin, Pin Han
AU - Tsai, Chang Shun
AU - Hsu, Chia Chien
AU - Lee, I. Ren
AU - Shen, Yu Xin
AU - Fan, Hsiu Fang
AU - Chen, Yun Wen
AU - Tu, Ling Hsien
AU - Liu, Wei Min
N1 - Funding Information:
This work is financially supported by the Ministry of Science and Technology, Taiwan [grant numbers: MOST109-2113-M-003-012 and MOST110-2113-M-003-021]. The authors gratefully acknowledge the Instrumentation Center of National Taiwan Normal University (High-Resolution Mass Spectrometer/JE OL, JMS-700, and Bruker Avance III HD-600 MHz) and for their support and assistance in this work. We thank the technical services provided by the “Bioimaging Core Facility of the National Core Facility for Biopharmaceuticals, National Science and Technology Council, Taiwan”. Thanks to Ya-Yun Yang and Ching-Yen Lin of Instrumentation Center, National Taiwan University for the assistance in TEM experiments. We also thank Hsiao-Chieh Tsai for collecting absorbance spectra.
Funding Information:
This work is financially supported by the Ministry of Science and Technology, Taiwan [grant numbers: MOST109-2113-M-003-012 and MOST110-2113-M-003-021]. The authors gratefully acknowledge the Instrumentation Center of National Taiwan Normal University (High-Resolution Mass Spectrometer/JE OL, JMS-700, and Bruker Avance III HD-600 MHz) and for their support and assistance in this work. We thank the technical services provided by the “Bioimaging Core Facility of the National Core Facility for Biopharmaceuticals, National Science and Technology Council, Taiwan”. Thanks to Ya-Yun Yang and Ching-Yen Lin of Instrumentation Center, National Taiwan University for the assistance in TEM experiments. We also thank Hsiao-Chieh Tsai for collecting absorbance spectra.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - The deposits of human islet amyloid polypeptide (IAPP), also called amylin, in the pancreas have been postulated to be a factor of pancreatic β-cell dysfunction and is one of the common pathological hallmarks of type II diabetes mellitus (T2DM). Therefore, it is imperative to gain an in-depth understanding of the formation of these aggregates. In this study, we demonstrate a rationally-designed strategy of an environmentally sensitive near-infrared (NIR) molecular rotor utilizing thioflavin T (ThT) as a scaffold for IAPP deposits. We extended the π delocalized system not only to improve the viscosity sensitivity but also to prolong the emission wavelength to the NIR region. A naphthalene moiety was also introduced to adjust the sensitivity of our designed probes to differentiate the binding microenvironment polarity of different targeted proteins. As a result, a novel NIR fluorogenic probe toward IAPP aggregates, namely AmySP-4-Nap-Ene, was first developed. When attached to different protein aggregates, this probe exhibited distinct fluorescence emission profiles. In a comparison with ThT, the fluorescence emission of non-ionic AmySP-4-Nap-Ene exhibits a significant difference between the presence of non-fibrillar and fibrillar IAPP and displays a higher binding affinity toward IAPP fibrils. Further, the AmySP-4-Nap-Ene can be utilized to monitor IAPP accumulating process and image fibrils both in vitro and in living cells.
AB - The deposits of human islet amyloid polypeptide (IAPP), also called amylin, in the pancreas have been postulated to be a factor of pancreatic β-cell dysfunction and is one of the common pathological hallmarks of type II diabetes mellitus (T2DM). Therefore, it is imperative to gain an in-depth understanding of the formation of these aggregates. In this study, we demonstrate a rationally-designed strategy of an environmentally sensitive near-infrared (NIR) molecular rotor utilizing thioflavin T (ThT) as a scaffold for IAPP deposits. We extended the π delocalized system not only to improve the viscosity sensitivity but also to prolong the emission wavelength to the NIR region. A naphthalene moiety was also introduced to adjust the sensitivity of our designed probes to differentiate the binding microenvironment polarity of different targeted proteins. As a result, a novel NIR fluorogenic probe toward IAPP aggregates, namely AmySP-4-Nap-Ene, was first developed. When attached to different protein aggregates, this probe exhibited distinct fluorescence emission profiles. In a comparison with ThT, the fluorescence emission of non-ionic AmySP-4-Nap-Ene exhibits a significant difference between the presence of non-fibrillar and fibrillar IAPP and displays a higher binding affinity toward IAPP fibrils. Further, the AmySP-4-Nap-Ene can be utilized to monitor IAPP accumulating process and image fibrils both in vitro and in living cells.
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U2 - 10.1016/j.talanta.2022.124130
DO - 10.1016/j.talanta.2022.124130
M3 - Article
C2 - 36462286
AN - SCOPUS:85145424893
SN - 0039-9140
VL - 254
JO - Talanta
JF - Talanta
M1 - 124130
ER -