Cyclic arylopeptoid oligomers: synthesis and conformational propensities of peptide-mimetic aromatic macrocycles

Abstract

Macrocyclic peptide-mimetic molecules are attracting renewed attention and have found widespread application in research fields ranging from biochemical science to materials science. Herein, we describe the synthesis and structural elucidation of cyclo[n]-p-arylopeptoids (classified into cyclic aromatic ε-amino acids) bearing various side chains, namely, C[n]pAP(Rn) (where n inside brackets denotes the number of main chain units and R inside parentheses represents side chains). We investigate the influence of n and R on the macrocyclization efficiency of linear p-arylopeptoid oligomers (n = 3, 4, 5) under high-dilution conditions with or without slow addition. The structures of the cyclo[4]-p-arylopeptoids (C[4]pAP(Rn)) and their conformational dynamics are disclosed on the basis of single-crystal X-ray analyses, viable-temperature (VT) 1H NMR studies, and density functional theory (DFT) calculations. We found two representative conformations (open and closed) of cyclo[4]-p-arylopeptoids (C[4]pAP(Rn)) in the solid state and whose preference in the solution state was most likely dependent on solvent polarity. We believe that this simple but dynamic macrocyclic peptide-mimetic molecular scaffold would be attractive for developing new functional molecular tools based on rational molecular design as well as molecular library screening strategies.

Self-Assembly of Supramolecular Architectures by the Effect of Amino Acid Residues of Quaternary Ammonium Pillar[5]arenes

“…There are additional cross-peaks between H 10 protons and H 8 protons of the methyl groups on the quaternarized nitrogen atom. It is also worth noting the presence of cross-peaks between spatially close H 4 protons of the amide group and H 8 , H 11 protons of the methyl groups and methyne fragment, respectively.…”

“…All the aqueous solutions were prepared with the Millipore-Q deionized water (>18.0 MΩ cm at 25 • C). (11) was prepared by a literature method [40].…”

“…In the literature on biomimetic structures capable of recognizing target analytes, synthetic analogues of peptides and proteins, which form a group of chemically and biologically related “platforms”, are the most convenient to employ. However, systems based on macrocyclic compounds are increasingly used to develop a new generation of peptidomimetics [ 9 , 10 , 11 ]. Macrocyclic structures offer great possibilities for geometry optimization of binding sites in the receptor in order to achieve complementarity between the “host” and the “guest”.…”

Peptoids as tools and sensors

“…However, as a direct result of only three coordinating oxygen atoms, sodium ion complexation was found to be weak and the molecules did not elicit transmembrane ion transportation. Hayakawa et al . used structurally similar N‐ substituted 4‐(aminomethyl)benzamide residues to produce cyclic extended arylopeptoids including a cyclo‐tetramer which was observed to undergo solvent dependent conformational change that may find application in some future molecular tools.…”

Recent advances in crystallization and self‐assembly of polypeptoid polymers

“…Ikeda and coworkers studied the influence of the number of backbone monomers and the chemical structures of side chains . It was found that there were two conformations, that is, all‐ cis ( cccc ) and cis‐trans alternating ( ctct ), coexisting in the solid state of polypeptoids.…”