Arginase Targeted Library
►Both catalyze the hydrolysis of L arginine to L ornithine and urea through a mechanism involving one hydroxide and two manganese ions
►Implicated in cancer immunosuppression and cancer tumor growth an increased metabolism of L Arg by myeloid derived suppressor cells producing Arg1 inhibits T lymphocyte response
►Other TIs include the following asthma, erectile dysfunction, cystic fibrosis, and atherosclerosis
►A strong binder is required to displace the hydroxide and replace it in the manganese coordination network
►X Ray structures of arginase cavity indicate a small volume, allowing little structural diversity between the metal coordinating and the amino acid moiety of the ligand
►Almost all the published Arg inhibitors exhibit insufficient differences in affinity to provide isoform selective inhibition in cultured cells or in vivo