Structural and functional mimicry of biopolymers and biomacromolecules are hot topics in chemical biology, medicinal chemistry and within biopharmaceuticals. Aryl-based foldamers represents one such interesting class of structural mimetics and our focus has been on the N-alkylated aromatic oligoamides, where the N-alkylation provides a facile and conceptually easy approach for introduction of appropriate structural diversity. In this study, we wish to present a new type of N-alkylated aminomethyl-aryloamides, termed arylopeptoids, with favorable physiochemical properties, improved aqueous solubility and pharmacokinetic stability based on biomimetic building blocks.
Initially, we have perceived the structural similarity between the arylopeptoid backbone and pharmaceutically relevant PPAR agonists, which led to the discovery of the first biologically active arylopeptoids. Here, we will present a methodology using microparticle matrix encoding of beads for targeting intrinsically disordered proteins (IDPs). IDPs represent an important and relatively unexplored class of proteins involved in signaling and regulatory functions and associated with many human diseases.
Arylopeptoids are “one-way sequence” oligoamides constructed from a mix of commercially available starting materials and biometic building blocks. The conformation around the amide bond can be controlled by the nature of the N-substituent and therefore offers promise for unique structural control of functional and structural bio-mimicry. Consequently, arylopeptoids might find use as proteomimetics or in biopharmaceutical applications. Likewise, arylopeptoids also show promise in mimicry of small-molecule drug structures and therefore as a drug discovery tool.