БНЗТ-2019

Novel approaches to the synthesis of high boron-loaded oligonucleotides for BNCT

Not scheduled

15m

Academpark

Speaker

Dr Darya Novopashina (Institute Chemical Biology and Fundamental Medicine)

Description

Boron neutron capture therapy (BNCT) is a promising therapeutic approach for the treatment of malignant tumors. Polyhedral boranes, such as boron clusters, attract considerable attention because they combine high boron content with relative metabolic inertness and low toxicity. Introduction of boron clusters to the oligonucleotide constructions permits to create agents for BNCT which can specifically interact with nucleic acids inside the cell. Three approaches for the conjugation of closo-dodecaborates to the oligonucleotides were proposed in this work: 1) A solid-phase approach based on the activation of free 5'-hydroxyl of protected immobilized oligonucleotides by N,N'-disuccinimidyl carbonate (DSC) with subsequent interaction with aminotetramethylene oxonium derivatives of closo-dodecaborate. 2) The activation of the 5'-phosphate group of oligonucleotide by reduction/oxidation pair thiphenylphosphine/ dipyridyldisulfide in the presence of dimethylaminopyridine in DMSO solution followed by interaction with aminotetramethylene oxonium derivatives of closo-dodecaborate. This approach permits to attach two closo-dodecaborate residues to the same oligonucleotide. 3) The click reaction between 5'-alkyne-modified oligonucleotides and azide-containing derivatives of closo-dodecaborate. The structures of all oligonucleotide conjugates bearing closo-dodecaborates were confirmed using MALDI-TOF mass spectrometry.

Summary

The proposed chemical methods of the synthesis of dodecaborate‐modified oligonucleotides are convenient for preparation of high boron-loaded oligonucleotides as potential agents for BNCT in cancer therapy.
This research was funded by Russian Scientific Foundation, grant number 19-74-20127.