Design, Expression, and Inhibitory Effects of Antagonistic Single-Chain Platelet-Derived Growth Factor on Lung Cancer Cells
Platelet-derived growth factor (PDGF) plays a pivotal role in numerous physiological and pathological conditions, acting as a dimeric disulfide-bound protein that induces receptor dimerization and subsequently activates cell signaling pathways. Given its involvement in various malignant and benign d...
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| Format: | Article |
| Language: | Arabic |
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Higher Commission for Scientific Research
2025-01-01
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| Series: | Syrian Journal for Science and Innovation |
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| Online Access: | https://journal.hcsr.gov.sy/archives/1540 |
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| _version_ | 1832586236359868416 |
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| author | Salim Alhafyan |
| author_facet | Salim Alhafyan |
| author_sort | Salim Alhafyan |
| collection | DOAJ |
| description | Platelet-derived growth factor (PDGF) plays a pivotal role in numerous physiological and pathological conditions, acting as a dimeric disulfide-bound protein that induces receptor dimerization and subsequently activates cell signaling pathways. Given its involvement in various malignant and benign diseases, targeting the PDGF signaling pathway is a promising therapeutic strategy. In this study, a single-chain antagonist PDGF (sc-PDGF) was designed by leveraging structural insights from the PDGF BB/receptor complex (PDB ID: 3JMG). The design involved substituting a receptor-binding site in one pole while keeping the other intact. Molecular dynamics simulations of the designed antagonistic sc-PDGF showed a noteworthy reduction in binding affinity at the mutant interface, indicating a reduced capability to effectively bind the receptor. The antagonistic sc-PDGF was successfully expressed in Escherichia coli, purified, and refolded using a one-step affinity chromatography approach. Far-UV circular dichroism spectroscopy demonstrated no significant alterations in the secondary structure of the designed sc-PDGF. Additionally, MTT assays confirmed the inhibitory effect of the sc-PDGF on lung cancer cells (A549), with an IC50 value of 0.72 µg/ml. This result underscores the potential of the sc-PDGF antagonist as a viable drug candidate for suppressing the proliferation of cancer cells, particularly those in which PDGF plays a critical role in cell growth. |
| format | Article |
| id | doaj-art-f49962ea3dbd484bbca9f1fe0221d21d |
| institution | Kabale University |
| issn | 2959-8591 |
| language | Arabic |
| publishDate | 2025-01-01 |
| publisher | Higher Commission for Scientific Research |
| record_format | Article |
| series | Syrian Journal for Science and Innovation |
| spelling | doaj-art-f49962ea3dbd484bbca9f1fe0221d21d2025-01-26T08:20:50ZaraHigher Commission for Scientific ResearchSyrian Journal for Science and Innovation2959-85912025-01-013110.5281/zenodo.14723413Design, Expression, and Inhibitory Effects of Antagonistic Single-Chain Platelet-Derived Growth Factor on Lung Cancer CellsSalim Alhafyan0University of Aleppo, Faculty of Technical Engineering, Dept. of Biotechnology Engineering_Aleppo_Syria.Platelet-derived growth factor (PDGF) plays a pivotal role in numerous physiological and pathological conditions, acting as a dimeric disulfide-bound protein that induces receptor dimerization and subsequently activates cell signaling pathways. Given its involvement in various malignant and benign diseases, targeting the PDGF signaling pathway is a promising therapeutic strategy. In this study, a single-chain antagonist PDGF (sc-PDGF) was designed by leveraging structural insights from the PDGF BB/receptor complex (PDB ID: 3JMG). The design involved substituting a receptor-binding site in one pole while keeping the other intact. Molecular dynamics simulations of the designed antagonistic sc-PDGF showed a noteworthy reduction in binding affinity at the mutant interface, indicating a reduced capability to effectively bind the receptor. The antagonistic sc-PDGF was successfully expressed in Escherichia coli, purified, and refolded using a one-step affinity chromatography approach. Far-UV circular dichroism spectroscopy demonstrated no significant alterations in the secondary structure of the designed sc-PDGF. Additionally, MTT assays confirmed the inhibitory effect of the sc-PDGF on lung cancer cells (A549), with an IC50 value of 0.72 µg/ml. This result underscores the potential of the sc-PDGF antagonist as a viable drug candidate for suppressing the proliferation of cancer cells, particularly those in which PDGF plays a critical role in cell growth.https://journal.hcsr.gov.sy/archives/1540: platelet-derived growth factor; pdgf; antagonist; cancer; molecular dynamics simulation; receptor dimerization; escherichia coli expression; mtt assay. |
| spellingShingle | Salim Alhafyan Design, Expression, and Inhibitory Effects of Antagonistic Single-Chain Platelet-Derived Growth Factor on Lung Cancer Cells Syrian Journal for Science and Innovation : platelet-derived growth factor; pdgf; antagonist; cancer; molecular dynamics simulation; receptor dimerization; escherichia coli expression; mtt assay. |
| title | Design, Expression, and Inhibitory Effects of Antagonistic Single-Chain Platelet-Derived Growth Factor on Lung Cancer Cells |
| title_full | Design, Expression, and Inhibitory Effects of Antagonistic Single-Chain Platelet-Derived Growth Factor on Lung Cancer Cells |
| title_fullStr | Design, Expression, and Inhibitory Effects of Antagonistic Single-Chain Platelet-Derived Growth Factor on Lung Cancer Cells |
| title_full_unstemmed | Design, Expression, and Inhibitory Effects of Antagonistic Single-Chain Platelet-Derived Growth Factor on Lung Cancer Cells |
| title_short | Design, Expression, and Inhibitory Effects of Antagonistic Single-Chain Platelet-Derived Growth Factor on Lung Cancer Cells |
| title_sort | design expression and inhibitory effects of antagonistic single chain platelet derived growth factor on lung cancer cells |
| topic | : platelet-derived growth factor; pdgf; antagonist; cancer; molecular dynamics simulation; receptor dimerization; escherichia coli expression; mtt assay. |
| url | https://journal.hcsr.gov.sy/archives/1540 |
| work_keys_str_mv | AT salimalhafyan designexpressionandinhibitoryeffectsofantagonisticsinglechainplateletderivedgrowthfactoronlungcancercells |