Thiol–yne ‘click’ chemistry as a route to functional lipid mimetics

Abstract

Thiol–alkyne ‘click’ chemistry is a modular, efficient mechanism to synthesize complex A₂B 3-arm star polymers. This general motif is similar to a phospholipid where the A blocks correspond to lypophilic chains and the B block represents the polar head group. In this communication we employ thiol–yne chemistry to produce polypeptide-based A₂B lipid mimetics. The utility of the thiol–yne reaction is demonstrated by using a divergent and a convergent approach in the synthesis. These polymers self-assemble in aqueous solution into spherical vesicles with a relatively narrow size distribution independent of block composition over the range studied. Using the thiol–yne convergent synthesis, we envision a modular approach to functionalize proteins or oligopeptides with lipophilic chains that can imbed seamlessly into a cell membrane.