Molecular Targeting of VEGF with a Suramin Fragment–DOCA Conjugate by Mimicking the Action of Low Molecular Weight Heparins
Molecular targeting of growth factors has shown great therapeutic potential in pharmaceutical research due to their roles in pathological conditions. In the present study, we developed a novel suramin fragment and deoxycholic acid conjugate (SFD) that exhibited the potential to bind to the heparin-b...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/1/46 |
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| author | Jooho Park Tae-Bong Kang Ji-Hong Lim Hyung-Sik Won |
| author_facet | Jooho Park Tae-Bong Kang Ji-Hong Lim Hyung-Sik Won |
| author_sort | Jooho Park |
| collection | DOAJ |
| description | Molecular targeting of growth factors has shown great therapeutic potential in pharmaceutical research due to their roles in pathological conditions. In the present study, we developed a novel suramin fragment and deoxycholic acid conjugate (SFD) that exhibited the potential to bind to the heparin-binding site (HBD) of vascular endothelial growth factor (VEGF) and to inhibit its pathogenic action for the first time. Notably, SFD was optimally designed for binding to the HBD of VEGF using the naphthalenetrisulfonate group, allowing to observe its excellent binding efficacy in a surface plasmon resonance (SPR) study, showing remarkable binding affinity (K<sub>D</sub> = 3.8 nM) as a small molecule inhibitor. In the tubular formation assay, it was observed that SFD could bind to HBD and exhibit antiangiogenic efficacy by inhibiting VEGF, such as heparins. The cellular treatment of SFD resulted in VEGF-inhibitory effects in human umbilical vein endothelial cells (HUVECs). Therefore, we propose that SFD can be employed as a novel drug candidate to inhibit the pathophysiological action of VEGF in diseases. Consequently, SFD, which has a molecular structure optimized for binding to HBD, is put forward as a new chemical VEGF inhibitor. |
| first_indexed | 2024-03-10T13:36:04Z |
| format | Article |
| id | doaj.art-ac9f1efa12a54f2f8aff0877ded44912 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T13:36:04Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-ac9f1efa12a54f2f8aff0877ded449122023-11-21T07:31:04ZengMDPI AGBiomolecules2218-273X2020-12-011114610.3390/biom11010046Molecular Targeting of VEGF with a Suramin Fragment–DOCA Conjugate by Mimicking the Action of Low Molecular Weight HeparinsJooho Park0Tae-Bong Kang1Ji-Hong Lim2Hyung-Sik Won3Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 27478, KoreaDepartment of Biotechnology, College of Biomedical & Health Science, Konkuk University, Chungju 27478, KoreaDepartment of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 27478, KoreaDepartment of Biotechnology, College of Biomedical & Health Science, Konkuk University, Chungju 27478, KoreaMolecular targeting of growth factors has shown great therapeutic potential in pharmaceutical research due to their roles in pathological conditions. In the present study, we developed a novel suramin fragment and deoxycholic acid conjugate (SFD) that exhibited the potential to bind to the heparin-binding site (HBD) of vascular endothelial growth factor (VEGF) and to inhibit its pathogenic action for the first time. Notably, SFD was optimally designed for binding to the HBD of VEGF using the naphthalenetrisulfonate group, allowing to observe its excellent binding efficacy in a surface plasmon resonance (SPR) study, showing remarkable binding affinity (K<sub>D</sub> = 3.8 nM) as a small molecule inhibitor. In the tubular formation assay, it was observed that SFD could bind to HBD and exhibit antiangiogenic efficacy by inhibiting VEGF, such as heparins. The cellular treatment of SFD resulted in VEGF-inhibitory effects in human umbilical vein endothelial cells (HUVECs). Therefore, we propose that SFD can be employed as a novel drug candidate to inhibit the pathophysiological action of VEGF in diseases. Consequently, SFD, which has a molecular structure optimized for binding to HBD, is put forward as a new chemical VEGF inhibitor.https://www.mdpi.com/2218-273X/11/1/46VEGFmolecular targetingdrug developmentsuraminheparin |
| spellingShingle | Jooho Park Tae-Bong Kang Ji-Hong Lim Hyung-Sik Won Molecular Targeting of VEGF with a Suramin Fragment–DOCA Conjugate by Mimicking the Action of Low Molecular Weight Heparins Biomolecules VEGF molecular targeting drug development suramin heparin |
| title | Molecular Targeting of VEGF with a Suramin Fragment–DOCA Conjugate by Mimicking the Action of Low Molecular Weight Heparins |
| title_full | Molecular Targeting of VEGF with a Suramin Fragment–DOCA Conjugate by Mimicking the Action of Low Molecular Weight Heparins |
| title_fullStr | Molecular Targeting of VEGF with a Suramin Fragment–DOCA Conjugate by Mimicking the Action of Low Molecular Weight Heparins |
| title_full_unstemmed | Molecular Targeting of VEGF with a Suramin Fragment–DOCA Conjugate by Mimicking the Action of Low Molecular Weight Heparins |
| title_short | Molecular Targeting of VEGF with a Suramin Fragment–DOCA Conjugate by Mimicking the Action of Low Molecular Weight Heparins |
| title_sort | molecular targeting of vegf with a suramin fragment doca conjugate by mimicking the action of low molecular weight heparins |
| topic | VEGF molecular targeting drug development suramin heparin |
| url | https://www.mdpi.com/2218-273X/11/1/46 |
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