Three Efficient Methods for Preparation of Coelenterazine Analogues.
The growing popularity of bioluminescent assays has highlighted the need for coelenterazine analogues possessing properties tuned for specific applications. However, the structural diversity of known coelenterazine analogues has been limited by current syntheses. Known routes for the preparation of coelenterazine analogues employ harsh reaction conditions that limit access to many substituents and functional groups. Novel synthetic routes reported here establish simple and robust methods for synthesis and investigation of structurally diverse marine luciferase substrates. Specifically, these new routes allow synthesis of coelenterazine analogues containing various heterocyclic motifs and substituted aromatic groups with diverse electronic substituents at the R(2) position. Interesting analogues described herein were characterized by their physicochemical properties, bioluminescent half-life, light output, polarity and cytotoxicity. Some of the analogues represent leads that can be utilized in the development of improved bioluminescent systems.
Promega Biosciences LLC, 277 Granada Drive, San Luis Obispo, CA, 93401, USA.
Anton
A
Shakhmin
Promega Corporation, 2800 Woods Hollow Road, Madison, WI, 53711-5399, USA.
Mary P
MP
Hall
Promega Biosciences LLC, 277 Granada Drive, San Luis Obispo, CA, 93401, USA.
Joel R
JR
Walker
Promega Corporation, 2800 Woods Hollow Road, Madison, WI, 53711-5399, USA.
Thomas
T
Machleidt
Promega Corporation, 2800 Woods Hollow Road, Madison, WI, 53711-5399, USA.
Brock F
BF
Binkowski
Promega Corporation, 2800 Woods Hollow Road, Madison, WI, 53711-5399, USA.
Keith V
KV
Wood
Promega Biosciences LLC, 277 Granada Drive, San Luis Obispo, CA, 93401, USA. thomas.kirkland@promega.com.
Thomas A
http://orcid.org/0000-0003-0859-5785
TA
Kirkland
bio-organic chemistry; coelenterazine analogues; luciferase; luminescence; nitrogen heterocycles