Tuning Hydrophobicity in Abiotic Affinity Reagents: Polymer Hydrogel Affinity Reagents for Molecules with Lipid-like Domains

Hydrophobic interactions often dominate the associative forces between biomacromolecules. A synthetic affinity reagent must be able to exploit and optimize these interactions. We describe synthesis of abiotic affinity reagents that sequester biomacromolecules with lipid-like domains. NIPAm-based copolymer nanoparticles (NPs) containing C4–C8 hydrophobic groups were evaluated for their affinity for lipopolysaccharides (LPS), the lipophilic component of the outer membrane of Gram-negative bacteria. Optimal affinity was found for NPs incorporating a linear C4 hydrocarbon group. 1D and 2D 1H NMR studies revealed that in water, the longer chain (C6 and C8) alkyl groups in the hydrogel NPs were engaged in intrachain association, rendering them less available to interact with LPS. Optimal LPS–NP interaction requires maximizing hydrophobicity, while avoiding side chain aggregation. Polymer compositions with high LPS binding were grafted onto agarose beads and evaluated for LPS clearance from solution; samples con...