Tyrosine-based asymmetric urea ligand for prostate carcinoma: Tuning biological efficacy through in silico studies |
| |
| Institution: | 1. Discipline of Chemistry, Indian Institute of Technology Indore, Khandwa Road, Simrol, Indore 453 552, India;2. Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Khandwa Road, Simrol, Indore 453 552, India;3. School of Pharmacy, Devi Ahilya University, Takshshila Campus, Khandwa Road, Indore 452 017, India;1. State Key Laboratory for Modification of Chemical Fibers and Polymers Materials & School of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China;2. College of Materials Sciences and Engineering, Donghua University, Shanghai 201620, China;3. School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, 273165, China;1. College of Materials Science and Engineering, Tongji University, Shanghai, 201804, China;2. State Key Laboratory of Crystal Materials, Shandong University, Jinan, 250100, China;3. School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, China;1. Department of Electricity and Energy, Vocational School, Bilecik Şeyh Edebali University, 11230, Bilecik, Turkey;2. Department of Chemistry, Faculty of Science, Ankara University, 06100, Beşevler, Ankara, Turkey;3. Department of Engineering Physics, Faculty of Engineering, Ankara University, 06100, Beşevler, Ankara, Turkey;4. Department of Chemistry, Faculty of Science and Literature, Sinop University, 57000, Sinop, Turkey |
| |
| Abstract: | In this article, we have explored the chemical interactions of tyrosine-based asymmetric urea ligands in the binding pockets of prostate specific membrane antigen (PSMA) through in silico studies. The S1 pocket of the PSMA protein offers better scope for modifications in the urea ligands to improve the binding affinity. Accordingly, tyrosine-based (S)-2-(3-((S)-1-carboxy-2-(4-(carboxymethoxy)phenyl)ethyl)ureido)pentanedioic acid (CYUE, 3) ligand was designed, synthesized and predicted to possess inhibition constant (Ki) of 55 nM with PSMA protein. The CYUE (3) ligand was further elaborated into a fluorescent diagnostic probe for detection of PSMA+ cancers. In vitro studies on human malignant cell lines such as LNCaP and PC-3 were performed to show the efficacy and specificity of the newly synthesized bio-construct. The fluorescent bio-conjugate was found to be very specific to the PSMA protein with an overall binding affinity constant (KD) of 88 nM. |
| |
| Keywords: | Tyrosine-based urea ligands PSMA Diagnostic probe |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
