TY - JOUR
T1 - Loop-mediated fluorescent probes for selective discrimination of parallel and antiparallel G-Quadruplexes
AU - Pandith, Anup
AU - Nagarajachari, Upendra
AU - Siddappa, Ravi Kumara Guralamatta
AU - Lee, Sungjin
AU - Park, Chin Ju
AU - Sannathammegowda, Krishnaveni
AU - Seo, Young Jun
N1 - Funding Information:
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (2017R1A2B4002398), funded by the Republic of Korea.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/4
Y1 - 2021/4
N2 - Herein we report simple pyridinium (1–3) and quinolinium (4) salts for the selective recognition of G-quadruplexes (G4s). Among them, the probe 1, interestingly, selectively discriminated parallel (c-KIT-1, c-KIT-2, c-MYC) G4s from anti-parallel/hybrid (22AG, HRAS-1, BOM-17, TBA) G4s at pH 7.2, through a switch on response in the far-red window. Significant changes in the absorption (broad 575 nm → sharp 505 nm) and emission of probe 1 at 620 nm, attributed to selective interaction with parallel G4s, resulted in complete disaggregation-induced monomer emission. Symmetrical push/pull molecular confinements across the styryl units in probe 1 enhanced the intramolecular charge transfer (ICT) by restricting the free rotation of C[dbnd]C units in the presence of sterically less hindered and highly accessible G4 surface/bottom tetrads in the parallel G4s, which is relatively lower extent in antiparallel/hybrid G4s. We confirm that the disaggregation of probe 1 was very effective in the presence of parallel G4–forming ODNs, due to the presence of highly available free surface area, resulting in additional π-stacking interactions. The selective sensing capabilities of probe 1 were analyzed using UV–Vis spectroscopy, fluorescence spectroscopy, molecular dynamics (MD)–based simulation studies, and 1H NMR spectroscopy. This study should afford insights for the future design of selective compounds targeting parallel G4s.
AB - Herein we report simple pyridinium (1–3) and quinolinium (4) salts for the selective recognition of G-quadruplexes (G4s). Among them, the probe 1, interestingly, selectively discriminated parallel (c-KIT-1, c-KIT-2, c-MYC) G4s from anti-parallel/hybrid (22AG, HRAS-1, BOM-17, TBA) G4s at pH 7.2, through a switch on response in the far-red window. Significant changes in the absorption (broad 575 nm → sharp 505 nm) and emission of probe 1 at 620 nm, attributed to selective interaction with parallel G4s, resulted in complete disaggregation-induced monomer emission. Symmetrical push/pull molecular confinements across the styryl units in probe 1 enhanced the intramolecular charge transfer (ICT) by restricting the free rotation of C[dbnd]C units in the presence of sterically less hindered and highly accessible G4 surface/bottom tetrads in the parallel G4s, which is relatively lower extent in antiparallel/hybrid G4s. We confirm that the disaggregation of probe 1 was very effective in the presence of parallel G4–forming ODNs, due to the presence of highly available free surface area, resulting in additional π-stacking interactions. The selective sensing capabilities of probe 1 were analyzed using UV–Vis spectroscopy, fluorescence spectroscopy, molecular dynamics (MD)–based simulation studies, and 1H NMR spectroscopy. This study should afford insights for the future design of selective compounds targeting parallel G4s.
KW - Disaggregation
KW - G-Quadruplexes
KW - Intramolecular charge transfer
KW - Molecular confinements
KW - Molecular dynamics
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U2 - 10.1016/j.bmc.2021.116077
DO - 10.1016/j.bmc.2021.116077
M3 - Article
C2 - 33631656
AN - SCOPUS:85101147976
SN - 0968-0896
VL - 35
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
M1 - 116077
ER -