Search anything and hit enter
  • Teams
  • Members
  • Projects
  • Events
  • Calls
  • Jobs
  • publications
  • Software
  • Tools
  • Network
  • Equipment

A little guide for advanced search:

  • Tip 1. You can use quotes "" to search for an exact expression.
    Example: "cell division"
  • Tip 2. You can use + symbol to restrict results containing all words.
    Example: +cell +stem
  • Tip 3. You can use + and - symbols to force inclusion or exclusion of specific words.
    Example: +cell -stem
e.g. searching for members in projects tagged cancer
Search for
Count
IN
OUT
Content 1
  • member
  • team
  • department
  • center
  • program_project
  • nrc
  • whocc
  • project
  • software
  • tool
  • patent
  • Administrative Staff
  • Assistant Professor
  • Associate Professor
  • Clinical Research Assistant
  • Full Professor
  • Graduate Student
  • Lab assistant
  • Non-permanent Researcher
  • Permanent Researcher
  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
  • Director of National Reference Center
  • Group Leader
  • Head of Facility
  • Head of Operations
  • Head of Structure
  • Honorary President of the Departement
  • Labex Coordinator
Content 2
  • member
  • team
  • department
  • center
  • program_project
  • nrc
  • whocc
  • project
  • software
  • tool
  • patent
  • Administrative Staff
  • Assistant Professor
  • Associate Professor
  • Clinical Research Assistant
  • Full Professor
  • Graduate Student
  • Lab assistant
  • Non-permanent Researcher
  • Permanent Researcher
  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
  • Director of National Reference Center
  • Group Leader
  • Head of Facility
  • Head of Operations
  • Head of Structure
  • Honorary President of the Departement
  • Labex Coordinator
Search
Go back
Scroll to top
Share
Starting Date
01
Mar 2015
Ending Date
01
Aug 2020
Status
Ongoing
Members
11
Structures
8
Publications
5

About

The use of light from the abyss in biology

 

In the last decades, bioluminescent systems based on the expression of a luciferase and the addition of a luciferin to monitor the emission of light have become very important tools for biological investigations. A growing proportion of these systems are using imidazo[1,2‑a]pyrazine luciferins such as the naturally-occurring coelenterazine (1) or the vargula luciferin (2) along with photoproteins or luciferases which came from sea creatures such as Aequorea, Renilla, Gaussia or Oplophorus.

Coelenterazine et Varguline

Central to the success of these tools are the synthetic pathways developed over the years to prepare not only these two endogenous substrates, but also analogues endowed with improved bioluminescent signals. And this took place along with extensive alteration of the corresponding luciferases leading to fairly efficient luciferin/luciferase reporting systems. Our contribution to this research domain has been, so far, the design of a new synthetic pathway which provided accesses to even more diverse imidazo[1,2‑a]pyrazines. Some of them turned out to be far more efficient substrates of specific luciferases in terms of signal  intensity or duration.

The following figure is illustrating some of our results. It depicts the superposition of the bioluminescence signals obtained with of 57 different imidazo[1,2‑a]pyrazine analogues over two hours, using nanoKAZ, an Oplophorus-derived luciferase. The red curve (Q01) happens to be the signal obtained with furimazine and compound Q108 is among our favorite.

 

 

Following a patent [1] many of these results are undergoing the process of being published [2-5]. Moreover, some of our luciferins analogues illustrated above can be made available for your research; do not hesitate to contact us.

In a next stage we are working on the design of small compounds endowed with a red-shifted chemiluminescence but still structurally related to these marine luciferins. The following picture of a 250 mL flask containing one of our chemiluminescent prototype is illustrating where we are now (the emission peaks at 605 nM).

We are still working on “dressing” such compounds with substituents which, for imidazo[1,2‑a] pyrazine-based compounds, are recognized by luciferases (this approach is very much like usual MedChem). From these we will then alter the luciferases currently using imidazo[1,2‑a]pyrazine luciferins so that these (completely original and eminently patentable) analogues become actual substrates of these enzyme. In case of success this would provide a fully original luciferin/luciferase reporting system endowed with a red (hopefully 605 nM) signal devoid of any prosthetic component such as fluorescent proteins or any other type of rather large constructions.

The hardest part in all this being (as usual) to get funding (very little luck so far).

Thank you for reading

 

1. Janin, Y. L.; Coutant, E. P.; Hervin, V.; Gagnot, G.; Jacob, Y.; Goyard, S.; Rose, T. Imidazopyrazine derivatives, process for preparation therof and their uses as luciferins. EP 3395803 / WO 2018197727, 2018.

2. Hervin, V.; Coutant, E. P.; Gagnot, G.; Janin, Y. L., Synthesis of alpha-amino esters via α-nitro or alpha-oxime esters, a review. Synthesis 2017, 49, 4093-4110.

3. Gagnot, G.; Hervin, V.; Coutant, E. P.; Desmons, S.; Baatallah, R.; Monnot, V.; Janin, Y. L., Synthesis of unnatural alpha-amino ethyl esters using ethyl nitroacetate and condensation or cycloaddition reactions. Beilstein J. Org. Chem. 2018, 14, 2846-2852.4.

4. Coutant, E. P.; Hervin, V.; Gagnot, G.; Ford, C.; Baatallah, R.; Janin, Y. L., Unnatural alpha-amino ethyl esters from diethylmalonate or ethyl beta-bromo-alpha-oxime carboxylate. Beilstein J. Org. Chem. 2018, 2853-2859.

5. Coutant, E. P.; Goyard, S.; Hervin, V.; Gagnot, G.; Baatallah, R.; Rose, T.; Jacob, Y.; Janin, Y. L., Gram-scale synthesis of luciferins derived from coelenterazine and original insights in their bioluminescence properties. Org. Biomol. Chem. 2019, doi: 10.1039/c9ob00459a.

 

 

 

 

Fundings

References