Synthesis and Binding Profile Using Simulations of New Building Blocks for PSMA Theranostics Against Prostate Cancer

GCPII also known as Prostate Specific Membrane Antigen (PSMA), is overexpressed in prostate cancer (PCa) cells and provide a biomarker for tumor targeting PSMA receptor. The development of lysine-urea-glutamate pharmacophore based inhibitors targeting PSMA for theranostics applications led to PSMA11 and PSMA617. In PSMA11, this pharmacophore is attached via aminohexanoic acid (Ahx) spacer to a chelator while in PSMA617 the pharmacophore is connecting with the linker 2-naphthyl-L-Ala, trans-4-(aminomethyl)cyclohexanecarboxylic acid and then to chelator. Here, we synthesized: (a) a squaramide analog of lysine-urea-glutamic acid; (b) two new building blocks for PSMA theranostics in which lysine-urea-glutamic acid was attached with two (i) phenyl alanine residues and (ii) amino hexanoic acid residues. Induced fit docking explored the binding profile of the new molecules. Biological experiments will provide data on the significance of the new molecules.