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Galactose Glycopolymer- Grafted Silica Nanoparticles: Synthesis and Binding Studies with Lectin.

Somdatta RudraSaradamoni MondalMithun ChakrabortyMusti J SwamyTushar Jana
Published in: ACS applied bio materials (2024)
Weak binding of carbohydrates with protein receptors possesses serious drawbacks in the advancement of therapeutics; however, the development of strategies for multipoint interactions between carbohydrates and protein can overcome these challenges. One such method is developed in this work where glycopolymer- grafted silica nanoparticles with a large number of carbohydrate units are prepared for the interactions with multiple binding sites of the protein. First, a glycomonomer, β-d-galactose-hydroxyethyl methacrylate (β-GEMA), was synthesized in a two-step process by coupling β-d-galactose pentaacetate and hydroxyethyl methacrylate (HEMA), followed by deacetylation for the preparation of poly(β-GEMA) glycopolymers (GPs). Further, the poly(β-GEMA) chains were grafted onto the silica nanoparticle (SiNP) surface by utilizing the " grafting - from " strategy of surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization to prepare p(β-GEMA)-grafted SiNPs (GNPs). Five different chain lengths ranging from 10 to 40 kDa of the GPs and the GNPs were prepared, and various characterization techniques confirmed the formation of GPs and grafting of the GPs on the SiNP surface. The particle size of GNPs and the number of GPs grafted on the SiNP surface showed a strong dependence on the chain length of the GPs. Further, the GNPs were subjected to a binding study with β-galactose-specific protein peanut agglutinin (PNA). A much stronger binding in the case of GNPs was observed with an association constant ∼320 times and ∼53 times than that of the monomeric methyl-β-d-galactopyranoside and the GPs, respectively. Additionally, the binding of the PNA with GNPs and GPs was also studied with varying chain lengths to understand the effects of the chain length on the binding affinity. A clear increase in binding constants was observed in the case of GNPs with increasing chain length of grafted GPs, attributed to the enhanced enthalpic and entropic contributions. This work holds its uniqueness in these improved interactions between carbohydrates and proteins, which can be used for carbohydrate-based targeted therapeutics.
Keyphrases
  • binding protein
  • dna binding
  • protein protein
  • small molecule
  • atrial fibrillation
  • mass spectrometry
  • ionic liquid
  • walled carbon nanotubes