Synthesis and self-assembly behaviour of poly(Nα-Boc-L-tryptophan)-block-poly(ethylene glycol)-block-poly(Nα-Boc-L-tryptophan)

We report for the first time the use of N alpha-Boc-L-tryptophan for the synthesis of amphiphilic BAB triblock copolymers for potential drug delivery applications. A library of poly(N alpha-Boc-L-tryptophan)-block-poly(ethylene glycol)-block-poly(N alpha-Boc-L-tryptophan) (PBocLTrp-b-PEG-b-PBocLTrp) amphiphilic copolymers were synthesized through the ring opening polymerization of N alpha-Boc-L-tryptophan N alpha-carboxy anhydride as initiated by diamino-terminated PEG of fixed molecular weight (M-n 3350). The influence of the hydrophobic block length over self-assembly was investigated for 4 of the BAB copolymers of molecular weights varying between M-n 5000 and M-n 17 000. It was found that an increase in hydrophobic block length led to an increase in hydrodynamic size of aggregates in solution, as well as a decrease in critical micelle concentration. TEM analysis showed the formation of spherical micelles with the largest of the copolymers forming interconnected networks of spherical micelles. The influence of hydrophobic block length over the formation of secondary structure was analyzed using circular dichroism and infrared spectroscopy. Collectively we found that the presence of t-Boc protected L-tryptophan leads to the preferential formation of alpha-helix secondary structure through hydrogen bonding, which, in a drug delivery vehicle context, could help in controlling drug release. Also, it is believed that the use of novel N alpha-Boc-L-tryptophan could improve drug stabilization in the hydrophobic core via pi-pi interactions between indole rings.