In vivo uptake of antisense oligonucleotide drugs predicted by ab initio quantum mechanical calculations.

ABSTRACT: Liver and kidney uptake and antisense activity is studied for a series of Locked Nucleic Acid (LNA) oligonucleotides with fully stereo-defined, internucleoside linkages. These stereo-specific phosphorothioates are made with a newly developed synthesis method and are being analyzed both theoretically and experimentally. Their structures are obtained theoretically by using many-body Schrödinger equations applied to a group of 11 stereo-defined LNA antisense oligonucleotides selected for biological experiments. The fully converged electronic structures were obtained from ab initio quantum calculations providing the specific electronic structures. One important result was the observation that the calculated electronic structure, represented by the iso-surface area of the electron density in Å<

SUBMITTER: Hansen HF 

PROVIDER: S-EPMC7973520 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature