Sandeep S. Naik

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

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.

Stimuli-Responsive Peptide-Based ABA-Triblock Copolymers: Unique Morphology Transitions With pH

We report the synthesis and solution characterization of poly(L-lysine)-b-poly(propylene oxide)-b-poly(L-lysine) (KPK) triblock copolymers with high lysine weight fractions (>75 wt%). In contrast to PK diblock copolymers in this composition range, KPK triblock copolymers exhibit morphology transitions as a function of pH. Using a combination of light-scattering and microscopy techniques, we demonstrate spherical micelle-vesicle and spherical micelle-disk micelle transitions for different K fractions. We interpret these morphology changes in terms of the energy penalty associated with folding the core P block to form a spherical micelle in relation to the interfacial curvature associated with different charged states of the K block.