Block length affects secondary structure, nanoassembly and thermosensitivity of poly(ethylene glycol)-poly(L-alanine) block copolymers

Poly(ethylene glycol)-conjugated polypeptides have been drawing attention as a biomaterial as well as a pharmaceutical agent. In this paper, we synthesized a series of poly(ethylene glycol)-poly(L-alanine) block copolymers (PEG-L-PA) and investigated the block length effect on (1) the secondary structure of the PA, (2) the nanostructure of the self-assembled amphiphilic PEG-L-PA, and (3) the thermosensitivity of the PEG-L-PA aqueous solution. First, the molecular weight of the L-PA was fixed at 700-760 Daltons and that of the conjugated PEG varied over 1,000, 2,000, and 5,000 Daltons. L-PA with an antiparallel beta-sheet structure in water transformed into an alpha-helical structure, and the self-assembled nanostructure of PEG-L-PA changed from a fibrous structure to a spherical micellar structure as the molecular weight of conjugated PEG increased. Then, when the molecular weight changed from 700 to 1,500 Daltons at a fixed molecular weight of PEG at 2,000, similar transitions involving antiparallel beta-sheets changing to alpha-helices, and fibers to spherical micelles were observed. The polymer aqueous solution underwent a sol-to-gel transition as the temperature increased in a high polymer concentration range of 3-14 wt%. Interestingly, the transition temperature did not follow the simple rule that a more hydrophobic polymer has a lower transition temperature. This paper suggests that the control of PEG molecular weight in PEG-conjugated polypeptide biomaterials is important in that it affects the secondary structure of the polypeptide, the nanoassembled morphology, and the thermosensitivity of the polymer.