Expedient Synthesis and Characterization of π-Extended Luciferins
Bioluminescence imaging enables the sensitive tracking of cell populations and the visualization of biological processes in living systems. Bioluminescent luciferase/luciferin pairs with far-red and near-infrared emission benefit from the reduced competitive absorption by blood and tissue while also facilitating multiplexing strategies. Luciferins with extended π-systems, such as AkaLumine and recently reported CouLuc-1 and -3, can be used for bioluminescence imaging in this long wavelength regime. Existing synthetic routes to AkaLumine and similar π-extended compounds require a multistep sequence to install the thiazoline heterocycle. Here we detail the development of a two-step strategy for accessing these molecules via a Horner-Wadsworth-Emmons reaction and cysteine condensation sequence from readily available aldehyde starting materials. We detail an improved synthesis of AkaLumine, as well as the corresponding two-carbon homologues, Tri- and Tetra-AkaLumine. We then extended this approach to prepare coumarin- and naphthalene-derived luciferins. These putative luciferins were tested against a panel of luciferases to identify capable emitters. Of these, an easily prepared naphthalene derivative exhibits photon emission on par with that of the broadly used Akaluc/AkaLumine pair with similar emission maxima. Overall, this chemistry provides efficient access to several bioluminescent probes for a variety of imaging applications.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
The Journal of organic chemistry - (2023) vom: 14. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Caldwell, Donald R [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 14.12.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1021/acs.joc.3c01920 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365868310 |
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| 245 | 1 | 0 | |a Expedient Synthesis and Characterization of π-Extended Luciferins |
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| 500 | |a Date Revised 14.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
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| 520 | |a Bioluminescence imaging enables the sensitive tracking of cell populations and the visualization of biological processes in living systems. Bioluminescent luciferase/luciferin pairs with far-red and near-infrared emission benefit from the reduced competitive absorption by blood and tissue while also facilitating multiplexing strategies. Luciferins with extended π-systems, such as AkaLumine and recently reported CouLuc-1 and -3, can be used for bioluminescence imaging in this long wavelength regime. Existing synthetic routes to AkaLumine and similar π-extended compounds require a multistep sequence to install the thiazoline heterocycle. Here we detail the development of a two-step strategy for accessing these molecules via a Horner-Wadsworth-Emmons reaction and cysteine condensation sequence from readily available aldehyde starting materials. We detail an improved synthesis of AkaLumine, as well as the corresponding two-carbon homologues, Tri- and Tetra-AkaLumine. We then extended this approach to prepare coumarin- and naphthalene-derived luciferins. These putative luciferins were tested against a panel of luciferases to identify capable emitters. Of these, an easily prepared naphthalene derivative exhibits photon emission on par with that of the broadly used Akaluc/AkaLumine pair with similar emission maxima. Overall, this chemistry provides efficient access to several bioluminescent probes for a variety of imaging applications | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Townsend, Katherine M |e verfasserin |4 aut | |
| 700 | 1 | |a Kolbaba-Kartchner, Bethany |e verfasserin |4 aut | |
| 700 | 1 | |a Hadjian, Tanya |e verfasserin |4 aut | |
| 700 | 1 | |a Ivanic, Joseph |e verfasserin |4 aut | |
| 700 | 1 | |a Love, Anna C |e verfasserin |4 aut | |
| 700 | 1 | |a Malvar, Beatrice |e verfasserin |4 aut | |
| 700 | 1 | |a Mills, Jeremy |e verfasserin |4 aut | |
| 700 | 1 | |a Prescher, Jennifer A |e verfasserin |4 aut | |
| 700 | 1 | |a Schnermann, Martin J |e verfasserin |4 aut | |
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