A practical method for the synthesis of peptoids containing both lysine-type and arginine-type monomers.

H L Bolt,S L Cobb

doi:10.1039/c5ob02279g

Abstract

Peptoids are a promising class of peptidomimetics that exhibit the key chemical and physical properties of peptides but without being hampered by susceptibility towards enzymatic degradation. Biologically active peptoids are often designed to be amphipathic in nature, consisting of hydrophobic monomers interspersed with either cationic lysine-type or arginine-type monomers. Access to amphipathic peptoids that contain both lysine-type and arginine-type monomers is highly desirable as it offers a route to further modulate the biological properties of this class of molecule. However, the lack of a suitable synthetic route to prepare mixed cationic peptoids has meant that their biological potential has remained almost largely unexplored. Herein, we present an efficient synthetic route that can be used to access novel cationic peptoids containing both lysine-type and arginine-type monomers within the same sequence.

Highlights

Peptoids are a promising class of peptidomimetics that exhibit the key chemical and physical properties of peptides but without being hampered by susceptibility towards enzymatic degradation
Active peptoids are often designed to be amphipathic in nature, consisting of hydrophobic monomers interspersed with either cationic lysine-type or arginine-type monomers
N-Boc protected amines are used in peptoid synthesis for the protection of amino groups, for example N-Boc 1,4-diaminobutane

Summary

Introduction

Peptoids are a promising class of peptidomimetics that exhibit the key chemical and physical properties of peptides but without being hampered by susceptibility towards enzymatic degradation. We present an efficient synthetic route that can be used to access novel cationic peptoids containing both lysine-type and arginine-type monomers within the same sequence. Polyarginine-type peptoids reported in the literature have generally been made using the method developed by Rothbard and co-workers.[13] This approach uses pyrazole-1-carboxamide to transform lysine-type monomers into their arginine-type analogs (i.e. an amino to guanido transformation).

Results

Conclusion