Exploring the Inhibitory Effects of Fucosylated Chondroitin Sulfate (FCS) Oligosaccharide Isolated from <i>Stichopus horrens</i> and the Derivatives on P-Selectin
Unique fucosylated chondroitin sulfate (FCS) extracted from the sea cucumber <i>Stichopus horrens</i> was subjected to deacetylation and deaminative depolymerization to generate oligosaccharide fragments containing anTal-diol, which were further purified to obtain the trisaccharide ShFCS...
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2025-05-01
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| Series: | Marine Drugs |
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| author | Caiyi Li Huifang Sun Xi Gu Wen Long Guangyu Zhu Xiaolu Wu Yu Wang Pengfei Li Le Sha Jiali Zhang Wenwu Sun Na Gao Zhili Zuo Jinhua Zhao |
| author_facet | Caiyi Li Huifang Sun Xi Gu Wen Long Guangyu Zhu Xiaolu Wu Yu Wang Pengfei Li Le Sha Jiali Zhang Wenwu Sun Na Gao Zhili Zuo Jinhua Zhao |
| author_sort | Caiyi Li |
| collection | DOAJ |
| description | Unique fucosylated chondroitin sulfate (FCS) extracted from the sea cucumber <i>Stichopus horrens</i> was subjected to deacetylation and deaminative depolymerization to generate oligosaccharide fragments containing anTal-diol, which were further purified to obtain the trisaccharide ShFCS-3. Subsequently, the coupling of ShFCS-3 and 4-azidoaniline was achieved by reductive amination. After purification, the main product ShFCS-A1 and by-product ShFCS-A2 were obtained, which were identified as (N-(L-Fuc<sub>2S4S</sub>-α1,3-D-GlcA-β1,3-D-anTalA<sub>4S6S</sub>-1-)-4-azidoaniline) and (4S)-[2-(3-L-Fuc<sub>2S4S</sub>-α1)-D-GlcA-β1]-2,4,5-trihydroxy-5-sulfated-pent-2-enoic-acid) by 1D/2D NMR spectroscopy, respectively. ELISA experiments revealed that ShFCS-A1 exhibited P-selectin inhibition rates of 19.73% ± 9.60% at 1 μM, 96.28% ± 2.37% at 10 μM, and near-complete inhibition (99.92% ± 0.84%) at 100 μM. ShFCS-A2 demonstrated inhibition rates of 8.29% ± 3.00% at 1 μM, 74.02% ± 8.80% at 10 μM, and maximal inhibition approaching 100% at 100 μM. Cellular-level experiments revealed that ShFCS-A1 and ShFCS-A2 inhibited P-selectin binding to HL-60 cells by 92.72% ± 0.85% and 96.97% ± 1.16% at 100 μM, respectively. Molecular docking analysis indicated binding energies of −5.954 kcal/mol for ShFCS-A1 and −6.140 kcal/mol for ShFCS-A2 with P-selectin, confirming their potent inhibitory effects. These findings highlight the therapeutic potential of FCS oligosaccharides as pharmacophores and provide an important foundation for developing novel small-molecule P-selectin inhibitors. |
| format | Article |
| id | doaj-art-beeb5aa650e54372b9d861f9ee8fc09c |
| institution | Kabale University |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj-art-beeb5aa650e54372b9d861f9ee8fc09c2025-08-20T03:27:28ZengMDPI AGMarine Drugs1660-33972025-05-0123623610.3390/md23060236Exploring the Inhibitory Effects of Fucosylated Chondroitin Sulfate (FCS) Oligosaccharide Isolated from <i>Stichopus horrens</i> and the Derivatives on P-SelectinCaiyi Li0Huifang Sun1Xi Gu2Wen Long3Guangyu Zhu4Xiaolu Wu5Yu Wang6Pengfei Li7Le Sha8Jiali Zhang9Wenwu Sun10Na Gao11Zhili Zuo12Jinhua Zhao13School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaSchool of Chemistry and Materials Science, South-Central Minzu University, Wuhan 430074, ChinaState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaCollege of Life Sciences, South-Central Minzu University, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, ChinaSchool of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, ChinaUnique fucosylated chondroitin sulfate (FCS) extracted from the sea cucumber <i>Stichopus horrens</i> was subjected to deacetylation and deaminative depolymerization to generate oligosaccharide fragments containing anTal-diol, which were further purified to obtain the trisaccharide ShFCS-3. Subsequently, the coupling of ShFCS-3 and 4-azidoaniline was achieved by reductive amination. After purification, the main product ShFCS-A1 and by-product ShFCS-A2 were obtained, which were identified as (N-(L-Fuc<sub>2S4S</sub>-α1,3-D-GlcA-β1,3-D-anTalA<sub>4S6S</sub>-1-)-4-azidoaniline) and (4S)-[2-(3-L-Fuc<sub>2S4S</sub>-α1)-D-GlcA-β1]-2,4,5-trihydroxy-5-sulfated-pent-2-enoic-acid) by 1D/2D NMR spectroscopy, respectively. ELISA experiments revealed that ShFCS-A1 exhibited P-selectin inhibition rates of 19.73% ± 9.60% at 1 μM, 96.28% ± 2.37% at 10 μM, and near-complete inhibition (99.92% ± 0.84%) at 100 μM. ShFCS-A2 demonstrated inhibition rates of 8.29% ± 3.00% at 1 μM, 74.02% ± 8.80% at 10 μM, and maximal inhibition approaching 100% at 100 μM. Cellular-level experiments revealed that ShFCS-A1 and ShFCS-A2 inhibited P-selectin binding to HL-60 cells by 92.72% ± 0.85% and 96.97% ± 1.16% at 100 μM, respectively. Molecular docking analysis indicated binding energies of −5.954 kcal/mol for ShFCS-A1 and −6.140 kcal/mol for ShFCS-A2 with P-selectin, confirming their potent inhibitory effects. These findings highlight the therapeutic potential of FCS oligosaccharides as pharmacophores and provide an important foundation for developing novel small-molecule P-selectin inhibitors.https://www.mdpi.com/1660-3397/23/6/236<i>Stichopus horrens</i>fucosylated chondroitin sulfatereductive aminationP-selectin |
| spellingShingle | Caiyi Li Huifang Sun Xi Gu Wen Long Guangyu Zhu Xiaolu Wu Yu Wang Pengfei Li Le Sha Jiali Zhang Wenwu Sun Na Gao Zhili Zuo Jinhua Zhao Exploring the Inhibitory Effects of Fucosylated Chondroitin Sulfate (FCS) Oligosaccharide Isolated from <i>Stichopus horrens</i> and the Derivatives on P-Selectin Marine Drugs <i>Stichopus horrens</i> fucosylated chondroitin sulfate reductive amination P-selectin |
| title | Exploring the Inhibitory Effects of Fucosylated Chondroitin Sulfate (FCS) Oligosaccharide Isolated from <i>Stichopus horrens</i> and the Derivatives on P-Selectin |
| title_full | Exploring the Inhibitory Effects of Fucosylated Chondroitin Sulfate (FCS) Oligosaccharide Isolated from <i>Stichopus horrens</i> and the Derivatives on P-Selectin |
| title_fullStr | Exploring the Inhibitory Effects of Fucosylated Chondroitin Sulfate (FCS) Oligosaccharide Isolated from <i>Stichopus horrens</i> and the Derivatives on P-Selectin |
| title_full_unstemmed | Exploring the Inhibitory Effects of Fucosylated Chondroitin Sulfate (FCS) Oligosaccharide Isolated from <i>Stichopus horrens</i> and the Derivatives on P-Selectin |
| title_short | Exploring the Inhibitory Effects of Fucosylated Chondroitin Sulfate (FCS) Oligosaccharide Isolated from <i>Stichopus horrens</i> and the Derivatives on P-Selectin |
| title_sort | exploring the inhibitory effects of fucosylated chondroitin sulfate fcs oligosaccharide isolated from i stichopus horrens i and the derivatives on p selectin |
| topic | <i>Stichopus horrens</i> fucosylated chondroitin sulfate reductive amination P-selectin |
| url | https://www.mdpi.com/1660-3397/23/6/236 |
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