(<i>S</i>)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic Acid as a Novel PSMA Targeting Scaffold for Prostate Cancer Imaging

Abstract

In an effort to seek novel agents targeting prostate-specific membrane antigen (PSMA), 16 ligands (<b>L1</b>-<b>L16</b>) with structural modifications in S1' binding pocket were synthesized and evaluated for PSMA inhibition. (<i>S</i>)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic acids proved to be potent PSMA ligands with <i>K</i>_i values ranging from 0.08 nM to 8.98 nM, which are in the range of or are higher in potency compared to previously published urea-based ligands. Computational docking was performed to study the binding mode of the two most potent ligands discovered. FITC-conjugated <b>L14</b> could selectively stain PSMA⁺ LNCaP cells over PSMA^- PC3 cells. IRDye800CW conjugated <b>L16</b> can effectively image tumors in a murine xenograft model of prostate cancer.