We investigated the functionalization of polymers with pedant ester groups by enzymatic transesterification. By detailed NMR analysis we have shown that while the monomer can be enzymatically modified, surprisingly no reaction was obtained upon polymerization. The results suggest that the formation of the enzyme-activated ester is hindered in the case of the polymer. This was overcome by the introduction of a spacer, thereby forming a polymer with two different pedant ester groups. NMR analysis confirmed high regioselectivity in the transesterification, namely the exclusive reaction on the distant ester group. We moreover combined two modes of selectivity, that is, regio-and stereoselectivity, by the kinetic resolution of a secondary alcohol in the functionalization of the polymer. This concept holds promises as it allows the design of materials with engineered-in highly selective reactivity toward enzymatic reactions.