Incorporating charged amino acid side chains in polypeptide polymer backbones to improve solubility usually leads to reduced secondary structuring. Here we show that highly water soluble (>15 mg.mL) β-sheets can be obtained via nucleotide monophosphate grafting onto simple poly(γ-propargyl- L-glutamate) backbone. This synthetic methodology has been applied to the synthesis of thymidine-based nucleopolypeptides presenting stable β-sheet conformation in aqueous solutions with pH values comprised between 4 and 8. These polymeric analogues of nucleoproteins exhibited selective interaction with simple DNA sequences displaying adenine.
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