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Potent and Selective Peptidyl Boronic Acid Inhibitors of the Serine Protease Prostate-Specific Antigen by Aaron M. LeBeau; Pratap Singh; John T. Isaacs; Samuel R. Denmeade is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Potent and Selective Peptidyl Boronic Acid Inhibitors of the Serine Protease Prostate-Specific Antigen about?

Prostate cancer cells produce high (microgram to milligram/milliliter) levels of the serine protease Prostate-Specific Antigen (PSA). PSA is enzymatically active in the extracellular fluid surrounding prostate cancers but is found at 1,000-to 10,000-fold lower concentrations in the circulation, where it is inactivated due to binding to abundant serum protease inhibitors. The exclusive presence of high levels of active PSA within prostate cancer sites makes PSA an attractive candidate for targeted imaging and therapeutics. A synthetic approach based on a peptide substrate identified first peptide aldehyde and then boronic acid inhibitors of PSA. The best of these had the sequence Cbz-Ser-Ser-Lys-Leu-(boro)Leu, with a K i for PSA of 65 nM. The inhibitor had a 60fold higher K i for chymotrypsin. A validated model of PSA's catalytic site confirmed the critical interactions between the inhibitor and residues within the PSA enzyme.

Who reads Potent and Selective Peptidyl Boronic Acid Inhibitors of the Serine Protease Prostate-Specific Antigen?

Author

Aaron M. LeBeau; Pratap Singh; John T. Isaacs; Samuel R. Denmeade

Publisher

Elsevier Science; Elsevier ; Cell Press; Elsevier BV (ISSN 1074-5521)

Published

2008

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)