Peptide-DNA Hybrid Selection for Chemical Functionality Recognition across Diverse Material Interfaces.

Abstract

Sequence-defined affinity ligands are powerful tools for molecular recognition, yet their selection has largely focused on defined molecular targets rather than shared chemical functionalities. Extending sequence-based recognition to a chemical moiety presents a distinct challenge because the same functionality must be recognized across structurally and chemically diverse molecular and material contexts. Here, we demonstrate that in vitro selection of peptide-DNA hybrids can generate an affinity ligand that recognizes a shared chemical functionality across distinct molecular and material interfaces. Using carboxylates as a model functionality, we selected a peptide-DNA hybrid library against a carboxylated material surface and identified R8rank1, whose enhanced binding depended on the selected DNA sequence functioning within the peptide-DNA hybrid architecture. R8rank1 hybrid preferentially recognized carboxylate-containing polymers with distinct molecular backbones over polymers bearing other functionalities, including an anionic sulfonate-containing polymer, and retained its recognition behavior across chemically distinct gold and silica nanoparticle interfaces presenting surface carboxylates. Fluorescently labeled R8rank1 further distinguished carboxylated from hydroxylated silica nanoparticles with an approximately eightfold difference in fluorescence and exhibited an apparent Kd of approximately 390 nM for the carboxylated surface, whereas the two surfaces were not significantly differentiated by zeta-potential measurements. This affinity-based readout provides chemical-functionality information complementary to conventional surface charge characterization. These findings extend sequence-based affinity selection from defined molecular targets to shared chemical functionalities and establish peptide-DNA hybrids as a selectable molecular recognition platform for identifying chemical functionalities across diverse material interfaces.

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