Journal article
Substrate specificity of prostate-specific membrane antigen
Bioorganic & medicinal chemistry, Vol.15(21), pp.6678-6686
2007
Handle:
https://hdl.handle.net/2376/112346
PMCID: PMC2014784
PMID: 17764959
Abstract
A series of potential PSMA substrates was prepared that explored acidic residues at the P1 position and various chromophores at the P2 position, while keeping the P1′ residue constant as
l-Glu. The substrate 4-phenylazobenzoyl-Glu-γ-Glu was found to be proteolyzed most efficiently.
A series of putative dipeptide substrates of prostate-specific membrane antigen (PSMA) was prepared that explored α- and β/γ-linked acidic residues at the P1 position and various chromophores at the P2 position, while keeping the P1′ residue constant as
l-Glu. Four chromophores were examined, including 4-phenylazobenzoyl, 1-pyrenebutyryl, 9-anthracenylcarboxyl-γ-aminobutyryl, and 4-nitrophenylbutyryl. When evaluating these chromophores, it was found that a substrate containing 4-phenylazobenzoyl at the P2 position was consumed most efficiently. Substitution at the P1 position with acidic residues showed that only γ-linked
l-Glu and
d-Glu were recognized by the enzyme, with the former being more readily proteolyzed. Lastly, binding modes of endogenous substrates and our best synthetic substrate (4-phenylazobenzoyl-Glu-γ-Glu) were proposed by computational docking studies into an X-ray crystal structure of the PSMA extracellular domain.
Metrics
7 Record Views
Details
- Title
- Substrate specificity of prostate-specific membrane antigen
- Creators
- Marc O Anderson - Department of Chemistry & Biochemistry, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USALisa Y Wu - Department of Chemistry & Biochemistry, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USANicholas M Santiago - Department of Chemistry & Biochemistry, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USAJamie M Moser - Department of Chemistry & Biochemistry, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USAJennifer A Rowley - Department of Chemistry & Biochemistry, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USAErin S.D Bolstad - Department of Chemistry, University of Montana, Missoula, MT 59812, USAClifford E Berkman - Department of Chemistry & Biochemistry, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USA
- Publication Details
- Bioorganic & medicinal chemistry, Vol.15(21), pp.6678-6686
- Academic Unit
- Chemistry, Department of
- Publisher
- Elsevier Ltd
- Identifiers
- 99900547511201842
- Language
- English
- Resource Type
- Journal article