Abstract
Abstract In nature, trehalose plays many roles, from bacterial signaling and immune cell activation through C-Type Lectin Receptors (CLRs) activated by trehalose-6,6′-dimycolate (cord factor), to the excipient properties of trehalose, which stabilizes organisms against extreme environmental conditions. To-date, our molecular understanding of trehalose has enabled the creation of synthetic trehalose analogues that are superior to the natural systems: trehalose-6,6′-dibehenate is an optimally active motif that retains CLR agonism, and polymers of 4,6-O-(4-vinylbenzylidene)-α,α-trehalose far out-perform the natural excipient abilities of trehalose. Here we report our results from combining these benefits to create synthetic copolymers of 4,6-O-(4-vinylbenzylidene)-trehalose and 4′,6′-O-(4-vinylbenzylidene)-trehalose-6-behenate by Reversible Addition-Fragmentation Chain Transfer Polymerization. The resulting alkylated trehalose copolymers are well defined (PDI < 1.4) with incorporation of behenic acid dispersed throughout the entire length of polymer as measured by DOSY-NMR. Overall, the copolymers retain the excipient properties of trehalose and enhance their ability to act as CLR agonists. A systematic exploration of the macromolecular parameters that drive CLR agonism (DP, PDI, and end-group chemistry), particularly through Dectin-1 and MINCLE, will be presented. These results suggest that alkylated trehalose copolymers could find use as dual vaccine adjuvants and stabilizing excipients.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call