Affinity-Selected Bicyclic Peptide G-Quadruplex Ligands Mimic a Protein-like Binding Mechanism.

ABSTRACT: The study of G-quadruplexes (G4s) in a cellular context has demonstrated links between these nucleic acid secondary structures, gene expression, and DNA replication. Ligands that bind to the G4 structure therefore present an excellent opportunity for influencing gene expression through the targeting of a nucleic acid structure rather than sequence. Here, we explore cyclic peptides as an alternative class of G4 ligands. Specifically, we describe the development of de novo G4-binding bicyclic peptides selected by phage display. Selected bicyclic peptides display submicromolar affinity to G4 structures and high selectivity over double helix DNA. Molecular simulations of the bicyclic peptide-G4 complexes corroborate the experimental binding strengths and reveal molecular insights into G

SUBMITTER: Liu KC 

PROVIDER: S-EPMC7212521 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature