Clickable Synthetic Polypeptides—Routes to New Highly Adaptive Biomaterials

Abstract

Synthetic polypeptides introduce a powerful capability to generate macromolecular species using the amino acid backbone found in nature, thus providing a route to biocompatible polymeric systems with highly programmable function. They can fold into stable secondary structures such as beta-sheets and α-helical structures, allowing the design of materials that optimally display surface groups that dictate cell signaling and molecular docking in biological systems and which undergo changes in chain stiffness and organization as well as complex hydrophobic and hydrophilic interactions that enable the intelligent design of responsive bioinspired materials. Until more recently, however, the versatility of these unique macromolecules was limited by the number, density, and type of functional groups which can be directly attached to the synthetic polypeptide backbone postpolymerization. In the past few years, researchers have introduced or utilized highly quantitative click chemistry to N-carboxy anhydride monomers used to generate synthetic polypeptide backbones, enabling direct and complete functionalization of macromolecular side-chains and side groups with a broader range of chemical functionality. These systems can yield charged polypeptides that exhibit pH responsive conformational changes and critical solution phase behavior, as well as densely grafted polypeptide macromolecules that mimic the behavior of naturally occurring proteins while introducing new function via facile synthetic modifications. Here we examine the significant advances in the design of bioinspired and biomimetic macromolecules presented by this capability, ranging from dynamic responsive micellar systems to biomimetic cell penetrating and antimicrobial peptides, and including structured hydrogel systems, and we look toward new possible areas of investigation and exploration utilizing the enabling combination of click chemistry with synthetic polypeptide materials.