کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1361874 | 981473 | 2007 | 9 صفحه PDF | دانلود رایگان |

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.
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.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 15, Issue 21, 1 November 2007, Pages 6678–6686