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| Title: | Tyrosine-based asymmetric urea ligand for prostate carcinoma: Tuning biological efficacy through in silico studies |
| Authors: | Sengupta, Sagnik Krishnan, Mena Asha Pandit, Amit Dudhe, Premansh Chelvam, Venkatesh |
| Keywords: | 2 [3 (1,3 dicarboxypropyl)ureido]pentanedioic acid;cyue;cyue rhodamine B conjugate;fluorescent dye;jb 7;prostate specific membrane antigen;tyrosine derivative;unclassified drug;urea derivative;yue;FOLH1 protein, human;glutamate carboxypeptidase II;ligand;membrane antigen;protein binding;tyrosine;urea;Article;binding affinity;binding site;cancer diagnosis;computer model;confocal laser scanning microscopy;drug design;drug protein binding;drug synthesis;fluorescence;human;human cell;hydrogen bond;in vitro study;inhibition constant;LNCaP cell line;male;molecular docking;PC-3 [Human prostate carcinoma] cell line;peptide synthesis;priority journal;prostate carcinoma;protein structure;quantitative structure activity relation;chemistry;computer simulation;confocal microscopy;diagnostic imaging;metabolism;pathology;procedures;prostate tumor;tumor cell culture;Antigens, Surface;Computer Simulation;Glutamate Carboxypeptidase II;Humans;Ligands;Male;Microscopy, Confocal;Prostatic Neoplasms;Protein Binding;Tumor Cells, Cultured;Tyrosine;Urea |
| Issue Date: | 2019 |
| Publisher: | Academic Press Inc. |
| Citation: | Sengupta, S., Krishnan, M. A., Pandit, A., Dudhe, P., Sharma, R., & Chelvam, V. (2019). Tyrosine-based asymmetric urea ligand for prostate carcinoma: Tuning biological efficacy through in silico studies. Bioorganic Chemistry, 91 doi:10.1016/j.bioorg.2019.103154 |
| 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. © 2019 Elsevier Inc. |
| URI: | https://doi.org/10.1016/j.bioorg.2019.103154 https://dspace.iiti.ac.in/handle/123456789/8876 |
| ISSN: | 0045-2068 |
| Type of Material: | Journal Article |
| Appears in Collections: | Department of Chemistry |
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