Ugi four-component polymerization of amino acid derivatives: a combinatorial tool for the design of polypeptoids

Abstract

Polypeptoids, consisting of nitrogen-substituted analogues of polypeptides, have become a real asset in modern sciences especially in the biomedical field. To address the increasing demand for polypeptoid structures with specific properties, this work explores the combinatorial character of the Ugi-four component polymerization of amino acid derivatives such as dipeptides and aminobutyric acid compounds with different aldehydes and isocyanides. A library of structurally diverse polypeptoids is prepared accordingly. Thermal and solution properties of the latter are characterized and discussed in a structure–property relationship approach highlighting the impact of both the backbone and side chains. Some materials demonstrate pH-responsiveness, thermo-responsiveness with tunable transition temperatures and biocompatibility. Given the great variety of possible substrates and the promising properties of the obtained polypeptoids, this straightforward and combinatorial strategy is attractive for the future development of polypeptoids and resulting applications.