New strategies for the design of folded peptoids revealed by a survey of noncovalent interactions in model systems.

Controlling the equilibria between backbone cis- and trans-amides in peptoids, or N-substituted glycine oligomers, constitutes a significant challenge in the construction of discretely folded peptoid structures. Through the analysis of a set of monomeric peptoid model systems, we have developed new and general strategies for controlling peptoid conformation that utilize local noncovalent interactions to regulate backbone amide rotameric equilibria, including n-->pi*, steric, and hydrogen bonding interactions. The chemical functionalities required to implement these strategies are typically confined to the peptoid side chains, preserve chirality at the side chain N-alpha-carbon known to engender peptoid structure, and are fully compatible with standard peptoid synthesis techniques.

Structure-function relationships in peptoids: recent advances toward deciphering the structural requirements for biological function.

Oligomers of N-substituted glycine, or peptoids, are versatile tools to probe biological processes and hold promise as therapeutic agents. An underlying theme in the majority of recent peptoid research is the connection between peptoid function and peptoid structure. For certain applications, well-folded peptoids are essential for activity, while unstructured peptoids appear to suffice, or even are superior, for other applications.

Synthesis and characterization of nitroaromatic peptoids: fine tuning peptoid secondary structure through monomer position and functionality.

N-substituted glycine oligomers, or peptoids, have emerged as an important class of foldamers for the study of biomolecular interactions and for potential use as therapeutic agents. However, the design of peptoids with well-defined conformations a priori remains a formidable challenge. New approaches are required to address this problem, and the systematic study of the role of individual monomer units in the global peptoid folding process represents one strategy.

Design and synthesis of macrocyclic peptomers as mimics of a quorum sensing signal from Staphylococcus aureus.

We report the design and synthesis of macrocyclic peptide-peptoid hybrids (peptomers) as analogs of autoinducing peptide I (AIP-I) from Staphylococcus aureus. Our solid-phase synthetic route includes efficient microwave-assisted reactions and a tandem macrocyclization-cleavage step, and we demonstrate its compatibility with parallel synthesis through the generation of a focused peptomer library. One of the peptomers was capable of stimulating biofilm formation in S.