Polypseudopeptides with Variable Stereochemistry: Synthesis via Click-Chemistry, Postfunctionalization, and Conformational Behavior in Solution

Abstract

Polypseudopeptides with well-defined stereochemistries have been synthesized from readily available amino-acid-based building blocks by connecting (l,l)- or (l,d)-dipeptide AB-monomers carrying azide and alkyne termini via triazole amide-isosteres efficiently formed in the course of the “click” reaction. Deprotection of the thus-prepared lysine-based polypseudopeptides of both all-(l)- and (d)-alt-(l)-stereochemistries afforded water-soluble polymers with ionizable amino side chains, which could be fully labeled with pyrene chromophores via quantitative amide bond formation. The conformational behavior of the deprotected as well as the pyrene-labeled polymers was investigated using UV/vis, CD, and fluorescence spectroscopies. On one hand, the free polyamines display pH-dependent conformations in water. On the other hand, the pyrene-labeled polypseudopeptides change their conformation in response to varying organic solvent composition. Whereas the strictly alternating polypseudopeptides structurally resemble channel-forming peptides, such as the Gramicidin family, the incorporation of (d)-configured amino acids as well as triazole amide-isosteres should lead to interesting new materials for bioapplications.