Identification of Sequence Selective Receptors for Peptides with a Carboxylic Acid Terminus

Abstract

Split-and-mix libraries of resin-bound "tweezer" receptors have been prepared and screened to identify receptors for dye-labelled tripeptides. The receptors incorporate a diamidopyridine unit to serve as a specific recognition site for the CO2H group, leading to strong and selective receptors for peptide guests with a CO2H terminus. The role of the dye-label, attached to the peptide guest to allow visualisation of selective recognition events in the screening experiments, has also been examined and was found to have a significant influence on the binding selectivities.

Effects of sequence context on the binding of tryptophan-containing peptides by the cucurbit[8]uril–methyl viologen complex

“…In any case, it is important to understand how the sequence environment (i.e., neighboring residues) influences binding. Several synthetic receptors have been shown to bind peptides and proteins (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), but in the majority of cases, these receptors are known to bind to a single type of residue, and the effects of sequence context are understood to a limited extent. This paper describes the effects of sequence context on the interactions of tryptophan-containing peptides with the synthetic receptor, cucurbit [8]uril (Q8), and a method that enables this determination in a rapid and parallel fashion.…”

Molecular tweezers for lysine and arginine – powerful inhibitors of pathologic protein aggregation

“…9–11 If a synthetic host molecule can be designed which exploits aromatic interactions for the specific recognition of single amino acid residues in peptides and proteins, it may be able to interfere in a predictable way with protein folding, aggregation or enzyme catalysis. Although a plethora of artificial receptor molecules have been developed for amino acids (e.g., crown ethers, 12–14 calixarenes, 15–19 cyclophanes, 20 polyaza-arenes, 21 galactose derivatives, 22 molecular tweezers with substituted phosphonate groups, 23 peptide units, 24 or porphyrine rings 25 as side walls), most of them provide little selectivity for a single residue. In this respect the molecular benzene tweezers 1 are remarkable, since they reject all other amino acids and only bind to lysine and arginine.…”

Sequence‐Selective Peptide Recognition with Designed Modules

“…Alternatively, the binding profile for a given host can be established by varying the sequence of its guest, which is often fluorescence-labelled. In recent years the groups of Wennemers, [4] Kilburn [5] and Schmuck [6] have developed their own optimized systems used for, for example, recognition of the Alzheimer's peptide, the d-Ala-d-Ala sequence and many more related small peptides. Very few attempts to create sequence-selective peptide receptors by rational design have been made.…”