Design and Synthesis of an Alkynyl Luciferin Analogue for Bioluminescence Imaging

Steinhardt, Rachel C.; O'Neill, Jessica M.; Rathbun, Colin M.; McCutcheon, David C.; Paley, Miranda A.; Prescher, Jennifer A.

doi:10.1002/chem.201503944

Cited by 30 publications

(26 citation statements)

References 63 publications

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“…This small molecule is the effective light emitter; thus, modifications to the scaffold can, in principle, impact both pharmacokinetic and spectral properties. There have been many notable successes in engineering unique luciferins in recent years . However, many of the scaffolds exhibit reduced photon outputs with luciferase, limiting their use in some cellular and tissue environments.…”

Section: Introductionmentioning

confidence: 99%

Pyridone Luciferins and Mutant Luciferases for Bioluminescence Imaging

2018

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New applications for bioluminescence imaging require an expanded set of luciferase enzymes and luciferin substrates. Here, we report two novel luciferins for use in vitro and in cells. These molecules comprise regioisomeric pyridone cores that can be accessed from a common synthetic route. The analogues exhibited unique emission spectra with firefly luciferase, although photon intensities remained weak. Enhanced light outputs were achieved by using mutant luciferase enzymes. One of the luciferin-luciferase pairs produced light on par with native probes in live cells. The pyridone analogues and complementary luciferases add to a growing set of designer probes for bioluminescence imaging.

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Section: Introductionmentioning

confidence: 99%

Pyridone Luciferins and Mutant Luciferases for Bioluminescence Imaging

2018

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“…), which have allowed the development of various practical applications. Thus, this system is currently being used routinely in biomedicine, bioanalysis and in a pharmaceutical setting …”

Section: Introductionmentioning

confidence: 99%

Interstate Crossing-Induced Chemiexcitation Mechanism as the Basis for Imidazopyrazinone Bioluminescence

2016

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Imidazopyrazinone dioxetanone is a central molecule in bioluminescence, as it is the scaffold responsible for light emission in many marine species. Herein, we have theoretically studied the thermolysis of its neutral and anionic forms. Our results allowed us to explain imidazopyrazinone bioluminescence with the Interstate Crossing‐Induced Chemiexcitation (ICIC) mechanism, and explain why neutral forms emit light efficiently to the contrary of anionic ones. Both forms decompose via a stepwise‐biradical pathway, but the biradical is formed either via an electron transfer (anion) or due to homolytic bond cleavage (neutral species). Absence of electron transfer leads to an entropic trap, a flat region where infinite possibilities for chemiexcitation exist. However, the resulting products can be in either triplet or singlet excited states. The triplet to singlet ratio is determined by the electron spin density distribution, which controls the rates of intersystem crossing.

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“…This difference is due to the strong electron‐donating effect and the increasing conjugation length of the ethynyl group. Not long ago, 5′‐C(CH) luciferin was synthesized and it indeed emits redshifted light with low intensity . The λ F values of the oLu analogues substituted with the fluorine atom and methyl group at either position show a small variation (no more than 15 nm), as the two substituents mainly have an inductive effect, no matter the electron‐withdrawing or ‐donating effect.…”

Section: Resultsmentioning

confidence: 99%

Theoretical Development of Near‐Infrared Bioluminescent Systems

Cheng

Liu

2018

Chemistry A European J

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The luciferin/luciferase system of the firefly has been used in bioluminescent imaging to monitor biological processes. In order to enhance the efficiency and expand the application range, some efforts have been made to tune the light emission, especially the effort to obtain NIR light. However, those case-by-case studies have not together revealed the nature and mechanism of the color tuning. In this paper, we theoretically investigated the fluorescence of all kinds of typical oxyluciferin analogues. The present systematical modifications of both oxyluciferin and luciferase indicate that the essential factor affecting the emission color is the charge distribution (or the electric dipole moment) on the oxyluciferin, which impacts on the charge transfer to form the light emitter and, subsequently, influence the strength and wavelength of the emission light. More negative charge distributed on the "thiazolone moiety" of the oxyluciferin or its analogues leads to a redshift. Based on this conclusion, we theoretically designed optimal pairs of luciferin analogue and luciferase for emitting NIR light, which could inspire new synthetic procedures and practical applications.

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Design and Synthesis of an Alkynyl Luciferin Analogue for Bioluminescence Imaging

Cited by 30 publications

References 63 publications

Pyridone Luciferins and Mutant Luciferases for Bioluminescence Imaging

Pyridone Luciferins and Mutant Luciferases for Bioluminescence Imaging

Interstate Crossing-Induced Chemiexcitation Mechanism as the Basis for Imidazopyrazinone Bioluminescence

Theoretical Development of Near‐Infrared Bioluminescent Systems

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