Utilizing Light to Control Glycopolymer–DC-SIGN Interactions via Molecular Motors

Molecular motors, known for their ability to undergo controlled unidirectional rotation under external stimuli, have gained growing interest for their potential applications in biological systems and smart materials. Meanwhile, glycosylated macromolecules are utilized in lectin-binding, making them potential candidates to combat pathogenesis, cancer, and biofilms. However, glycopolymers are limited by their current inability to adapt in response to external stimuli, restricting their potential for future precision therapies. By integrating multivalent glycopolymeric structures with first-generation molecular rotary motors, it becomes possible to control carbohydrate-lectin interactions using intrinsic motor functions. Herein, we present photoadaptive glycopolymer-based first-generation molecular motors functionalized with immunologically important monosaccharides, β-d-glucopyranoside and β-d-mannopyranoside. The lectin-binding properties were subsequently investigated using surface plasmon resonance with DC-SIGN and Langerin, key players within the human innate immune system. Additionally, a competition assay with the envelope glycoprotein of HIV, namely gp120, was conducted to ascertain the inhibitory potential of these photoresponsive glycopolymer-based molecular motors. It was established that the light-controlled conformation of the molecular motor impacted both the overall binding affinity and half-maximal inhibitory concentration values. These findings create opportunities to control the binding affinity of glycopolymers and emphasize the potential of light-driven glycopolymers to modulate key interactions in cell-specific targeted delivery of therapeutics.