PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.

PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.

PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.

PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.

PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.

PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.

PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.

PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.

PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.

PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.

PSMA, also known as glutamate carboxypeptidase 2 or folate hydrolase 1, is highly expressed in nearly all prostate cancers. Structurally, PSMA is a large extracellular carboxypeptidase domain that is tethered to the cellular membrane by a short transmembrane domain. Physiologically, PSMA is also expressed in normal tissue, including non-malignant prostate tissue, the kidney, the small intestine, and the central nervous system. In most tissues, PSMA likely contributes to folate uptake by cleaving the C-terminal glutamate from folic acid (Figure 1). Within the brain, PSMA regulates the level of N-acetylaspartylglutamate (NAAG) by catalyzing its degradation to glutamate. Structure of PSMA substrates and inhibitors. Left: structure of the PSMA substrate folic acid. The peptide bond (dashed box) linking the P1 glutamate residue (blue) to the remainder of the substrate (P1, red) is cleaved by PSMA. Right: Structure of the PSMA-PET agents 18F-DCFPyL and 68Ga-PSMA-11. The scissile peptide bond has been replaced by a non-hydrolyzable urea motif (red) to generate PMSA inhibitors. The P1 glutamate residue is essential for binding to PSMA, but a wide degree of variability is tolerated in the opposing end of the structure.