α-Glucan derivatives as selective blockers of aldolase A : Computer-aided structure optimization and the effects on HCC
Copyright © 2023 Elsevier Ltd. All rights reserved..
Aldolase A (ALDOA) promotes hepatocellular carcinoma (HCC) growth and is a potential therapeutic target. A previous study found an α-D-glucan (α-D-(1,6)-Glcp-α-D-(1,4)-Glcp, 10.0:1.0), named HDPS-4II, that could specifically inhibit ALDOA but its activity was not high enough. In this study, the derivatives of α-D-glucan binding to ALDOA were optimized using molecular docking, and its sulfated modification demonstrated the highest affinity with ALDOA among sulfated, carboxylated, and aminated derivatives. Sulfated HDPS-4II and dextrans with different molecular weights (1000 Da, 3000 Da, and 4000 Da) were prepared. Using MST assay, 3-O-sulfated HDPS-4II (SHDPS-4II) and 1000 Da dextran (SDextran1) showed higher affinities to ALDOA with Kd of 1.83 μM and 85.04 μM, respectively. Furthermore, SHDPS-4II and SDextran1 markedly inhibited the proliferation of HCC cells both in vitro and in vivo by blocking ALDOA. These results demonstrate that sulfated modification of α-D-glucans could enhance their affinities with ALDOA and anti-HCC effects.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 2023 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:325 |
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| Enthalten in: |
Carbohydrate polymers - 325(2023) vom: 01. Feb., Seite 121566 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xiao, Qian-Han [VerfasserIn] |
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| Links: |
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| Themen: |
Aldolase A |
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| Anmerkungen: |
Date Completed 28.11.2023 Date Revised 28.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.carbpol.2023.121566 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364996862 |
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| 520 | |a Aldolase A (ALDOA) promotes hepatocellular carcinoma (HCC) growth and is a potential therapeutic target. A previous study found an α-D-glucan (α-D-(1,6)-Glcp-α-D-(1,4)-Glcp, 10.0:1.0), named HDPS-4II, that could specifically inhibit ALDOA but its activity was not high enough. In this study, the derivatives of α-D-glucan binding to ALDOA were optimized using molecular docking, and its sulfated modification demonstrated the highest affinity with ALDOA among sulfated, carboxylated, and aminated derivatives. Sulfated HDPS-4II and dextrans with different molecular weights (1000 Da, 3000 Da, and 4000 Da) were prepared. Using MST assay, 3-O-sulfated HDPS-4II (SHDPS-4II) and 1000 Da dextran (SDextran1) showed higher affinities to ALDOA with Kd of 1.83 μM and 85.04 μM, respectively. Furthermore, SHDPS-4II and SDextran1 markedly inhibited the proliferation of HCC cells both in vitro and in vivo by blocking ALDOA. These results demonstrate that sulfated modification of α-D-glucans could enhance their affinities with ALDOA and anti-HCC effects | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Aldolase A | |
| 650 | 4 | |a Glucan | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a Holotrichia diomphalia | |
| 650 | 4 | |a Sulfated derivant | |
| 650 | 7 | |a Fructose-Bisphosphate Aldolase |2 NLM | |
| 650 | 7 | |a EC 4.1.2.13 |2 NLM | |
| 650 | 7 | |a Glucans |2 NLM | |
| 650 | 7 | |a Hydrolases |2 NLM | |
| 650 | 7 | |a EC 3.- |2 NLM | |
| 700 | 1 | |a Li, Ze-Zhi |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Shu-Yao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiao-Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Hong-Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Qiao, Rui-Zhi |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Wen-Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jing-Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Guang-Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Dian-Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Ke-Han |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Wei |e verfasserin |4 aut | |
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