The synthesis of two novel, water-soluble, sugar-substituted poly(p-phenyleneethynylene)s and their interactions with concanavalin A (Con A) and bacteria (Escherichia coli) are reported, and the issue of sensitivity enhancement is investigated. Both sugar-substituent PPEs (P5 and P7) exhibited strong interactions with Con A with K-SV values exceeding 10(8) M-1. The binding constants between the sugar-substituted polymers and Con A were also quantitatively calculated using isothermal titration calorimetry (ITC) resulting in association constants as high as 10(6) M-1. P5 and P7 strongly interact with mannose-binding E. coli, which led to their aggregation.