Effective cytotoxic action of classical folate analogues against tumor cells (1,2) relies not only on their potent inhibition of the primary intracellular target—analogues have been tailored to inhibit dihydrofolate reductase, thymidylate synthase, and glycinamide ribonucleotide formyl transferase—but also on their efficiently mediated internalization and subsequent conversion to poly-g-glutama...

We have synthesized a biologically inert, photosensitive derivative of the major excitatory amino acid, L-glutamate (which we call MDNI-glu) that makes more efficient use of incident light than all other caged glutamates. Laser flash photolysis of MDNI-glu in acutely isolated hippocampal brain slices evoked a rapid increase in intracellular Ca2+ concentration in astrocytes.

Proteins may undergo a type of posttranslational modification - polyglutamylation, where a glutamate residue is enzymatically linked to the γ-carboxyl group of a glutamate in the primary sequence of proteins and additional glutamates are then sequentially added via α-carboxyl-linkages to the growing glutamate side chain. Nna1 (a.k.a. CCP1) defines the 6-member cytosolic carboxypeptidase (CCP) f...