Homogeneous Oligomeric Ligands Prepared via Radical Polymerization that Recognize and Neutralize a Target Peptide

Abstract

Abiotic ligands that bind to specific biomolecules have attracted attention as substitutes for biomolecular ligands, such as antibodies and aptamers. Radical polymerization enables the production of robust polymeric ligands from inexpensive functional monomers. However, little has been reported about the production of monodispersed polymeric ligands. Herein, we present homogeneous ligands prepared via radical polymerization that recognize epitope sequences on a target peptide and neutralize the toxicity of the peptide. Taking advantage of controlled radical polymerization and separation, a library of multifunctional oligomers with discrete numbers of functional groups was prepared. Affinity screening revealed that the sequence specificity of the oligomer ligands strongly depended on the number of functional groups. The process reported here will become a general step for the development of abiotic ligands that recognize specific peptide sequences.

Properties and applications of precision oligomer materials; where organic and polymer chemistry join forces

“…The target peptides could be immobilized on beads and loaded into a chromatography column with the synthetized oligomers separated according to their interactions with the respective peptides (refer to Section 3.3.2). 108 …”

“…The target peptides could be immobilized on beads and loaded into a chromatography column with the synthetized oligomers separated according to their interactions with the respective peptides (refer to Section 3.3.2). 108 Hybrid methodologies that combine stepwise strategies with purification of oligomer mixtures have recently been developed and offer gains when compared to traditional approaches, especially to higher molecular weight systems. This is exemplified by the synthesis of welldefined conjugated materials by Otsubo and coworkers.…”

“…The combination of living polymerization and chromatographic separation was also employed by Hoshino and coworkers while studying the molecular recognition of the peptide melittin by synthetic oligomers 108 . A library of discrete BCOs consisting of oAA (deprotection of oTBA) and oNIPAM blocks was synthesized via RAFT and chromatography purification.…”

“…The combination of living polymerization and chromatographic separation was also employed by Hoshino and coworkers while studying the molecular recognition of the peptide melittin by synthetic oligomers. 108 A library of discrete BCOs consisting of oAA (deprotection of oTBA) and oNIPAM blocks was synthesized via RAFT and chromatography purification. In the next step, an aggregation essay was performed to investigate interactions with melittin to identify recognition according to F I G U R E 2 1 (a) Schematic overview over the catalytic reaction pathway, (b) view of cooperative interactions in soluble and supported sequence-defined catalytic oligomers and (c) catalytic activity of TIP, ITP, sTIP, and sITP in the aerobic oxidation of benzyl alcohol.…”

Controlling the block sequence of multi-block oligomer ligands for neutralization of a target peptide

“…Sequence specificity was observed in the case of homogeneous di-block oligomers of A and T. 20 A di-block hexamer consisting of 4 units of A and 2 units of T recognize negatively charged KRKR sequence on melittin, though, the hexamer consisting of 2 units of A and 4 units of T recognized hydrophobic amino acids including tryptophan next to the KRKR sequence. 20 These results demonstrated that the synthetic oligomer ligands, which effectively interact with the target peptide via multi-modal interactions, can be prepared by controlling the block sequence of the multi-functional oligomers. Screening of mono-, di-, and tri-block oligomer ligands revealed that not only the localization and combination of functional groups but also the sequence of the functional block and end groups are of importance to design high affinity ligands that binds and neutralize activity of target biomacromolecules.…”