Modular synthesis of cell-permeating 2-ketoglutarate esters.
Cell-permeating esters of 2-ketoglutarate (2-KG) have been synthesized through a convergent sequence from two modules in two and three steps, respectively. This route provides access to a full series of mono- and disubstituted 2-KG esters, enabling us to define the effect of regioisomeric masking on metabolite release and antihypoxic activity in cell-based assays. In addition to providing insight into the biological activity of cell permeable 2-KG esters, the straightforward and modular nature of this synthetic route may prove useful for the development of next-generation 2-KG analogues for diagnostic and therapeutic applications.
Chemical Biology Laboratory, National Cancer Institute, Frederick, Maryland 21702, United States.
Thomas T
TT
Zengeya
Chemical Biology Laboratory, National Cancer Institute, Frederick, Maryland 21702, United States.
Rhushikesh A
RA
Kulkarni
Chemical Biology Laboratory, National Cancer Institute, Frederick, Maryland 21702, United States.
Jordan L
JL
Meier
D001686:Biological Phenomena; D002463:Cell Membrane Permeability; D004952:Esters; D007656:Ketoglutaric Acids / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D004952:Esters; D007656:Ketoglutaric Acids