| Title |
The molecular pruning of a phosphoramidate peptidomimetic inhibitor of prostate-specific membrane antigen
|
|---|---|
| Published in |
Bioorganic & Medicinal Chemistry, August 2007
|
| DOI | 10.1016/j.bmc.2007.07.028 |
| Pubmed ID | |
| Authors |
Lisa Y. Wu, Marc O. Anderson, Yoko Toriyabe, Jack Maung, Tammy Y. Campbell, Cheryl Tajon, Marat Kazak, Jamie Moser, Clifford E. Berkman |
| Abstract |
To identify the pharmacophore of a phosphoramidate peptidomimetic inhibitor of prostate-specific membrane antigen (PSMA), a small analog library was designed and screened for inhibitory potency against PSMA. The design of the lead inhibitor was based upon N-acyl derivatives of endogenous substrate folyl-gamma-Glu and incorporates a phosphoramidate group to interact with the PSMA catalytic zinc atoms. The scope of the analog library was designed to test the importance of various functional groups to the inhibitory potency of the lead phosphoramidate. The IC(50) for the lead phosphoramidate inhibitor was 35 nM while the IC(50) values for the analog library presented a range from 0.86 nM to 4.1 microM. Computational docking, utilizing a recently solved X-ray crystal structure of the recombinant protein, along with enzyme inhibition data, was used to propose a pharmacophore model for the PSMA active site. |
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Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 3% |
| Unknown | 35 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 10 | 28% |
| Student > Bachelor | 5 | 14% |
| Researcher | 4 | 11% |
| Other | 2 | 6% |
| Lecturer | 2 | 6% |
| Other | 5 | 14% |
| Unknown | 8 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 9 | 25% |
| Biochemistry, Genetics and Molecular Biology | 7 | 19% |
| Agricultural and Biological Sciences | 5 | 14% |
| Arts and Humanities | 2 | 6% |
| Immunology and Microbiology | 2 | 6% |
| Other | 3 | 8% |
| Unknown | 8 | 22% |