Predicting Diagnostic Potential of Cathepsin in Epithelial Ovarian Cancer: A Design Validated by Computational, Biophysical and Electrochemical Data
Background: Epithelial ovarian cancer remains one of the leading variants of gynecological cancer with a high mortality rate. Feasibility and technical competence for screening and detection of epithelial ovarian cancer remain a major obstacle and the development of point of care diagnostics (POCD)...
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MDPI AG
2021-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/1/53 |
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| author | Hemangi Ranade Priya Paliwal Anis Ahmad Chaudhary Sakshi Piplani Hassan Ahmed Rudayni Mohammed Al-Zharani Ravi Ranjan Niraj Manali Datta |
| author_facet | Hemangi Ranade Priya Paliwal Anis Ahmad Chaudhary Sakshi Piplani Hassan Ahmed Rudayni Mohammed Al-Zharani Ravi Ranjan Niraj Manali Datta |
| author_sort | Hemangi Ranade |
| collection | DOAJ |
| description | Background: Epithelial ovarian cancer remains one of the leading variants of gynecological cancer with a high mortality rate. Feasibility and technical competence for screening and detection of epithelial ovarian cancer remain a major obstacle and the development of point of care diagnostics (POCD) may offer a simple solution for monitoring its progression. Cathepsins have been implicated as biomarkers for cancer progression and metastasis; being a protease, it has an inherent tendency to interact with Cystatin C, a cysteine protease inhibitor. This interaction was assessed for designing a POCD module. Methods: A combinatorial approach encompassing computational, biophysical and electron-transfer kinetics has been used to assess this protease-inhibitor interaction. Results: Calculations predicted two cathepsin candidates, Cathepsin K and Cathepsin L based on their binding energies and structural alignment and both predictions were confirmed experimentally. Differential pulse voltammetry was used to verify the potency of Cathepsin K and Cathepsin L interaction with Cystatin C and assess the selectivity and sensitivity of their electrochemical interactions. Electrochemical measurements indicated selectivity for both the ligands, but with increasing concentrations, there was a marked difference in the sensitivity of the detection. Conclusions: This work validated the utility of dry-lab integration in the wet-lab technique to generate leads for the design of electrochemical diagnostics for epithelial ovarian cancer. |
| first_indexed | 2024-03-10T01:51:23Z |
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| id | doaj.art-c3c96273da694bcbb59dd8ab517e4d1e |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T01:51:23Z |
| publishDate | 2021-12-01 |
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| series | Biomolecules |
| spelling | doaj.art-c3c96273da694bcbb59dd8ab517e4d1e2023-11-23T13:06:19ZengMDPI AGBiomolecules2218-273X2021-12-011215310.3390/biom12010053Predicting Diagnostic Potential of Cathepsin in Epithelial Ovarian Cancer: A Design Validated by Computational, Biophysical and Electrochemical DataHemangi Ranade0Priya Paliwal1Anis Ahmad Chaudhary2Sakshi Piplani3Hassan Ahmed Rudayni4Mohammed Al-Zharani5Ravi Ranjan Niraj6Manali Datta7Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur 303002, IndiaAmity Institute of Biotechnology, Amity University Rajasthan, Jaipur 303002, IndiaDepartment of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh 11564, Saudi ArabiaVaxine Pty Ltd., Flinders University, Bedford Park, SA 5042, AustraliaDepartment of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh 11564, Saudi ArabiaDepartment of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh 11564, Saudi ArabiaAmity Institute of Biotechnology, Amity University Rajasthan, Jaipur 303002, IndiaAmity Institute of Biotechnology, Amity University Rajasthan, Jaipur 303002, IndiaBackground: Epithelial ovarian cancer remains one of the leading variants of gynecological cancer with a high mortality rate. Feasibility and technical competence for screening and detection of epithelial ovarian cancer remain a major obstacle and the development of point of care diagnostics (POCD) may offer a simple solution for monitoring its progression. Cathepsins have been implicated as biomarkers for cancer progression and metastasis; being a protease, it has an inherent tendency to interact with Cystatin C, a cysteine protease inhibitor. This interaction was assessed for designing a POCD module. Methods: A combinatorial approach encompassing computational, biophysical and electron-transfer kinetics has been used to assess this protease-inhibitor interaction. Results: Calculations predicted two cathepsin candidates, Cathepsin K and Cathepsin L based on their binding energies and structural alignment and both predictions were confirmed experimentally. Differential pulse voltammetry was used to verify the potency of Cathepsin K and Cathepsin L interaction with Cystatin C and assess the selectivity and sensitivity of their electrochemical interactions. Electrochemical measurements indicated selectivity for both the ligands, but with increasing concentrations, there was a marked difference in the sensitivity of the detection. Conclusions: This work validated the utility of dry-lab integration in the wet-lab technique to generate leads for the design of electrochemical diagnostics for epithelial ovarian cancer.https://www.mdpi.com/2218-273X/12/1/53cathepsin-cystatinmolecular dynamicsdifferential pulse voltammetry |
| spellingShingle | Hemangi Ranade Priya Paliwal Anis Ahmad Chaudhary Sakshi Piplani Hassan Ahmed Rudayni Mohammed Al-Zharani Ravi Ranjan Niraj Manali Datta Predicting Diagnostic Potential of Cathepsin in Epithelial Ovarian Cancer: A Design Validated by Computational, Biophysical and Electrochemical Data Biomolecules cathepsin-cystatin molecular dynamics differential pulse voltammetry |
| title | Predicting Diagnostic Potential of Cathepsin in Epithelial Ovarian Cancer: A Design Validated by Computational, Biophysical and Electrochemical Data |
| title_full | Predicting Diagnostic Potential of Cathepsin in Epithelial Ovarian Cancer: A Design Validated by Computational, Biophysical and Electrochemical Data |
| title_fullStr | Predicting Diagnostic Potential of Cathepsin in Epithelial Ovarian Cancer: A Design Validated by Computational, Biophysical and Electrochemical Data |
| title_full_unstemmed | Predicting Diagnostic Potential of Cathepsin in Epithelial Ovarian Cancer: A Design Validated by Computational, Biophysical and Electrochemical Data |
| title_short | Predicting Diagnostic Potential of Cathepsin in Epithelial Ovarian Cancer: A Design Validated by Computational, Biophysical and Electrochemical Data |
| title_sort | predicting diagnostic potential of cathepsin in epithelial ovarian cancer a design validated by computational biophysical and electrochemical data |
| topic | cathepsin-cystatin molecular dynamics differential pulse voltammetry |
| url | https://www.mdpi.com/2218-273X/12/1/53 |
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