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Structure-activity relationships of 2',5'-oligoadenylate analogue modifications of prostate-specific membrane antigen
Xinning Wang1, Haibin Tian, Zhenghong Lee
1Department of Cancer Biology , Cleveland Clinic, Cleveland, Ohio 44195, USA.
Abstract:
Prostate-specific membrane antigen (PSMA) is an ideal biomarker for prostate cancer. A previously reported 2-5A conjugate RBI1033 (3) showed binding affinity more than 10 times higher than the parent urea-based compound (S)-2-(3-((S)-5-amino-1-carboxypentyl)ureido) pentanedioic acid (1). The purpose of this work is to further optimize the structure of 3 to identify highly selective ligands of PSMA. It was found that conjugates having 2-5A in their structure showed extraordinary improved binding affinity to PSMA compared with compound 1. Removal of 2-5A significantly reduced its biological activity. The results will provide a path to agents for targeted imaging and treatment of prostate cancer.
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