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.

A Water‐Soluble Peptoid Chelator that Can Remove Cu2+ from Amyloid‐β Peptides and Stop the Formation of Reactive Oxygen Species Associated with Alzheimer's Disease

“…Interestingly, we have recently shown that the incorporation of one or more piperazine units within the backbone of hydrophobic peptoids ensures their water-solubility, while maintaining their sequence and structure. [27] Capitalizing on these findings, we present here a new, water-soluble and helical peptoid chelator, which is selective for Cu 2+ , and describe how we applied it for the removal of Cu 2+ from Ab peptides, in aqueous medium, in order to stop the formation of ROS associated with AD, including in presence of Zn 2+ .…”

A Water‐Soluble Peptoid Chelator that Can Remove Cu2+ from Amyloid‐β Peptides and Stop the Formation of Reactive Oxygen Species Associated with Alzheimer's Disease

“…As a result, P1 is hydrophobic and water insoluble, properties that limit its utilization as a drug candidate, despite its selectivity to Cu 2+ . Interestingly, we have recently shown that the incorporation of one or more piperazine units within the backbone of hydrophobic peptoids ensures their water‐solubility, while maintaining their sequence and structure [27] . Capitalizing on these findings, we present here a new, water‐soluble and helical peptoid chelator, which is selective for Cu 2+ , and describe how we applied it for the removal of Cu 2+ from Aβ peptides, in aqueous medium, in order to stop the formation of ROS associated with AD, including in presence of Zn 2+ .…”

Increasing the Functional Group Diversity in Helical β-Peptoids: Achievement of Solvent- and pH-Dependent Folding

“…In our previous study, we observed a positive effect on solubility as well as a retained folding propensity when incorporating a piperazine-containing N-terminal capping group, 55 as originally reported by Maayan and co-workers. 75 We therefore decided to add this feature to all oligomer designs in the current study. It was also decided to apply the previously developed synthetic strategy based on trimer segment couplings.…”