Sequence-Selective Binding of Oligopeptides in Water through Hydrophobic Coding

Abstract

A general method for sequence-specific binding of peptides remains elusive despite decades of research. By creating an array of “hydrophobically coded dimples” on the surface of a surface–core doubly cross-linked micelle, we synthesized water-soluble nanoparticle receptors to recognize peptides by the location, number, and nature of their hydrophobic side chains. Minute differences in the side chains could be distinguished and affinities up to 20 nM were obtained for biologically active oligopeptides in water.

Imprinted micelles for chiral recognition in water: shape, depth, and number of recognition sites

“…Using this technique, we have created strong and selective receptors for a number of different guests including bile salt derivatives, 30 aromatic carboxylates and sulfonates, 31–33 nonsteroidal anti-inflammatory drugs (NSAIDs), 34 carbohydrates, 35, 36 and oligopeptides. 37 …”

Peptide-Binding Nanoparticle Materials with Tailored Recognition Sites for Basic Peptides

“…Given the exceptional selectivity in binding for leucine/isoleucine and phenylalanine/tyrosine, the polymerization and cross-linking in the confined nanospace of micelle must be extremely amenable to imprinting. 43 …”

“…In our previous work, even glycine was found to influence the imprinting and binding of peptides, despite its lack of a side chain. 43 MINPs contain multiple functional groups including numerous triazole, hydroxyl, ammonium, and amide. These groups can certainly interact with the bound peptide through hydrogen bonds, van der Waals interactions, cationic–π interactions, and electrostatic interactions.…”

“…Using micellar imprinting, a technique developed in our laboratory, 42 we created molecularly imprinted nanoparticles (MINPs) with high affinity (as low as 20 nM in water) and exceptional selectivity for peptides 2–12 residues in length. 43 Recognition was based on imprinted “hydrophobic dimples” created on the surface of the cross-linked micelle that complement the hydrophobic side chains of the templating peptide in size and shape. These “dimples” essentially encoded the MINP receptors with molecular recognition information for the peptide guests and were precise enough to distinguish leucine and isoleucine, as well as phenylalanine and tyrosine that differ by one hydroxyl.…”

“…These “dimples” essentially encoded the MINP receptors with molecular recognition information for the peptide guests and were precise enough to distinguish leucine and isoleucine, as well as phenylalanine and tyrosine that differ by one hydroxyl. 43 …”