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O 6 ‐Alkylguanine DNA Alkyltransferase Mediated Disassembly of a DNA Tetrahedron
Author(s) -
Copp William,
Wilds Christopher J.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202002565
Subject(s) - dna , phosphodiester bond , deoxyribose , oligonucleotide , dna nanotechnology , chemistry , deoxyguanosine , dna clamp , dna ligase , a dna , stereochemistry , biochemistry , biophysics , biology , gene , rna , reverse transcriptase
Tetrahedron DNA structures were formed by the assembly of three‐way junction ( TWJ ) oligonucleotides containing O 6 ‐2′‐deoxyguanosine‐alkylene‐ O 6 ‐2′‐deoxyguanosine (butylene and heptylene linked) intrastrand cross‐links (IaCLs) lacking a phosphodiester group between the 2′‐deoxyribose residues. The DNA tetrahedra containing TWJs were shown to undergo an unhooking reaction by the human DNA repair protein O 6 ‐alkylguanine DNA alkyltransferase (hAGT) resulting in structure disassembly. The unhooking reaction of hAGT towards the DNA tetrahedra was observed to be moderate to virtually complete depending on the protein equivalents. DNA tetrahedron structures have been explored as drug delivery platforms that release their payload in response to triggers, such as light, chemical agents or hybridization of release strands. The dismantling of DNA tetrahedron structures by a DNA repair protein contributes to the armamentarium of approaches for drug release employing DNA nanostructures.