Insights into the molecular mechanism of dextran sulfate inhibiting DNA digestion by pepsin: a crucial role of sulfate group on the binding to DNA

Jing Zhang, Leshan Ding, Hu Hou, Long Yu, Jing Li, Ping Dong

Research output: Contribution to journalArticlepeer-review

Abstract

Sulfate polysaccharides can inhibit DNA digestion in simulated gastric juice in vitro, which is important for regulating dietary nucleic acids metabolism, but the mechanism of inhibition is unclear. This study used dextran sulfate (DS) with different sulfate groups and molecular weights to explore the effect of DS on DNA digestion. Molecular interactions between DS and DNA were investigated by biolayer interferometry (BLI), isothermal titration calorimetry (ITC) and molecular dynamics simulations. Results indicated that DS with higher molecular weight and sulfate group content showed stronger inhibitory effect of DNA digestion. ITC results showed that the combined Kd value of DNA and DS was about 2.53 mM. The main reason for inhibition of DNA digestion is that the formation of hydrogen bonds between the sulfate group of DS and DNA bases hinders the binding of DNA to pepsin. This finding will facilitate new strategies for nucleic acid metabolism and oral drug delivery.

Original languageEnglish
Pages (from-to)498-504
Number of pages7
JournalJournal of Biomolecular Structure and Dynamics
Volume43
Issue number1
Early online date17 Nov 2023
DOIs
Publication statusPublished - 2025
Externally publishedYes

Keywords

  • dextran sulfate
  • DNA digestion
  • inhibitory effect
  • interaction
  • molecular mechanism

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