Physicochemical aspects of solid phase synthesis using cross-linked polymeric matrices

Solid phase synthesis (SPS) offers a bottom-up approach for assembling (bio-)oligomers and polymers with precise molecular detail. Although SPS has been applied to various organic compounds, it is expressly convenient for assembling biopolymers. Fundamental studies and optimization efforts have focused solely on organic chemistry aspects, often neglecting physicochemical issues. Here, we summarize the current understanding of the physical phenomena occurring in the gel-like, solvent-swollen polymer beads used commonly as a solid support, aiming to help advance SPS by providing new insights based on physicochemical principles.