Structures of annexin A2-PS DNA complexes show dominance of hydrophobic interactions in phosphorothioate binding.

ABSTRACT: The introduction of phosphorothioate (PS) linkages to the backbone of therapeutic nucleic acids substantially increases their stability and potency. It also affects their interactions with cellular proteins, but the molecular mechanisms that underlie this effect are poorly understood. Here, we report structural and biochemical studies of interactions between annexin A2, a protein that does not possess any known canonical DNA binding domains, and phosphorothioate-modified antisense oligonucleotides. We show that a unique mode of hydrophobic interactions between a sulfur atom of the phosphorothioate group and lysine and arginine residues account for the enhanced affinity of modified nucleic acid for the protein. Our results demonstrate that this mechanism of interaction is observed not only

SUBMITTER: Hyjek-Skladanowska M 

PROVIDER: S-EPMC9943651 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature