Macrocyclic Tetramers—Structural Investigation of Peptide-Peptoid Hybrids

Abstract

Outstanding affinity and specificity are the main characteristics of peptides, rendering them interesting compounds for basic and medicinal research. However, their biological applicability is limited due to fast proteolytic degradation. The use of mimetic peptoids overcomes this disadvantage, though they lack stereochemical information at the α-carbon. Hybrids composed of amino acids and peptoid monomers combine the unique properties of both parent classes. Rigidification of the backbone increases the affinity towards various targets. However, only little is known about the spatial structure of such constrained hybrids. The determination of the three-dimensional structure is a key step for the identification of new targets as well as the rational design of bioactive compounds. Herein, we report the synthesis and the structural elucidation of novel tetrameric macrocycles. Measurements were taken in solid and solution states with the help of X-ray scattering and NMR spectroscopy. The investigations made will help to find diverse applications for this new, promising compound class.

Pyrvinium Pamoate: Past, Present, and Future as an Anti-Cancer Drug

“…Polyamines analogs and peptide/peptoid-like structures have been proposed as promising anti-cancer compounds [ 1 , 2 , 3 , 4 , 5 , 6 ]. Cyanine dyes share structural similarities to several lipophilic polyamines [ 7 , 8 ], polyaminopyrimidines [ 9 ], and mitochondrial-targeting peptoids [ 10 ]. Pyrvinium is a cyanine dye with multiple amino groups with similarities to some naturally occurring polyaminopyrimidine/polyamine compounds.…”