Incorporation of Chemoselective Functionalities into Peptoids via Solid-Phase Submonomer Synthesis

Abstract

A simple route to the introduction of a number of chemoselective functional groups into peptoids (oligo(N-substituted glycines)) by an extension of the standard solid-phase submonomer method is reported. The following groups were introduced: aminooxyacetamide, N-(carbamoylmethyl)acetohydrazide, mercaptoacetamide, 2-pyridinesulfenylmercaptoacetamide, and aldehyde-terminated peptoids. The method uses commercially available reagents, is fully compatible with standard peptoid submonomer synthesis conditions, is easily automated, and generates the desired functionalized peptoid in high yield and purity. Peptoids with suitable pairs of chemoselective ligation groups were joined in high yield.

Recent Progress in the Design of Monodisperse, Sequence-Defined Macromolecules

“…Furthermore, larger moieties, such as carbohydrates, dyes, cofactors or chiral monomers, that induce the formation of secondary structures, were used . In order to achieve attachment of the peptoid to other molecules, chemoselective coupling partners, such as ketones, aldehydes or thiols were applied . The incorporation of large moieties, like metal complexes and hormones to a peptoid backbone was moreover demonstrated by Kirshenbaum et al, who coupled the moieties and the peptoid by click chemistry .…”

“…[117] In order to achieve attachment of the peptoid to other molecules, chemoselective coupling partners, such as ketones, aldehydes or thiols were applied. [128] The incorporation of large moieties, like metal complexes and hormones to a peptoid backbone was moreover demon strated by Kirshenbaum et al, who coupled the moieties and the peptoid by click chemistry. [129] The syntheses are usually conducted in milligram scales and nearly quanti tative yields can be achieved.…”

Peptoid-based hierarchically-structured biomimetic nanomaterials: Synthesis, characterization and applications

“…1b). Because several hundreds of commercially available amines can be used for peptoid synthesis, this method provides the access to a nearly infinite diversity of peptoid sequences with precisely controlled side-chain chemistries, allowing a fine tuning of the structure and function of peptoid-based nanomaterials by incorporating protein-like high information content into the materials design [3,20,21].…”

Peptoids: Emerging Therapeutics for Neurodegeneration

“…Peptoids are synthesized with relative ease and at comparatively low cost 10,11 . While peptoids can be constructed to mimic peptides in side-chain chemistry, a direct sequence translation is not always the most effective approach.…”