Water soluble hydrophobic peptoids via a minor backbone modification

Abstract

Peptoids – oligomers of N-substituted glycine – are an important class of peptide mimics that are widely used in areas ranging from biology and medicine to metal binding and catalysis. The utility of peptoids, however, especially for applications in aqueous solutions, is often hampered by the hydrophobic nature of their sequences dictated by structural and functional requirements. Herein we describe a simple method to solubilize hydrophobic peptoids in water without modifying their original sequences, via the insertion of biocompatible and low cost piperazine or homopiperazine groups at the N- or C-terminus of the peptoid backbone. We show that our method can be applied for the production of α-, β- and azapeptoids, which display high water solubility for long periods of time. Moreover, circular dichroism (CD) spectroscopy revealed that the incorporation of piperazine groups within α-peptoids, having chiral naphthyl monomers, β-peptoids and unstructured azapeptoids results in peptoids that exhibit high conformational order in water.