Synthetic Progress toward PBLG–PLA Alternating Rod–Coil Polymers with Discrete and Disperse α-Helical Rod Segments

Poly(γ-benzyl-L-glutamate) (PBLG)-based rod–coil polymers are attractive platforms for self-assembly because PBLG adopts an α-helical conformation and behaves as a rigid polypeptide rod. However, conventional PBLG-containing assemblies often rely on amphiphilic contrast with hydrophilic blocks such as poly(ethylene glycol) (PEG), which can obscure the contribution of PBLG helix–helix association. In addition, PBLG segments prepared by N-carboxyanhydride ring-opening polymerization (NCA ROP) possess inherent rod-length dispersity, which may affect the packing and morphology of assembled structures.

To investigate helix-driven self-assembly in a non-PEG system, we designed PBLG–PLA alternating rod–coil polymers in which PBLG rods are periodically connected by lactide-based polyester coil spacers. PLA was selected as a biodegradable coil spacer that modulates PBLG rod spacing without introducing strong PEG-like amphiphilic micellization. To control the PBLG rod length precisely, we targeted a discrete BLG32 oligomer as a molecularly defined α-helical rod segment with uniform contour length. Two complementary synthetic approaches were explored: iterative exponential growth (IEG) for discrete BLG/PBLG rod segments and NCA ROP for disperse PBLG segments. Using the IEG strategy, BLG oligomer growth was demonstrated up to BLG64 from an AB-type BLG building block bearing allyl ester and Boc-protected amine groups, and a defined BLG7 oligomer was also prepared.

This work establishes synthetic routes toward PBLG–PLA alternating rod–coil polymers containing either discrete or disperse α-helical rod segments. The resulting platform will enable future comparison of PBLG helix-driven self-assembly as a function of rod-length dispersity, providing insight into how molecular precision in secondary-structured rod segments influences morphology formation.