Sequence-defined peptoids via iterative exponential growth

Abstract

Synthetic control over polymer sequence, composition, and stereochemistry is critical to understanding their influence on the intramolecular and intermolecular interactions of polymers. We report an iterative exponential growth (IEG) strategy for peptoids, a class of sequence-defined peptidomimetics, relying on orthogonally protected monomers. The IEG technique enables the synthesis of monodisperse peptoids with varied sequences, side chains, and stereoconfigurations on a scale that is useful for material science applications. The method allows for direct monitoring of the reaction progress without the need for cleavage from a solid-support. This IEG strategy offers higher molecular weights than other solution-phase sequence-defined synthetic strategies for peptoids and seeks to mimic the precise structural organization of sequence-defined biopolymers for a synthetic polymer system, which we anticipate will enable the rational design of functional polymer materials.