bc300074k_si_001.pdf (4.11 MB)
Cross-Linked DNA: Site-Selective “Click” Ligation in Duplexes with Bis-Azides and Stability Changes Caused by Internal Cross-Links
journal contribution
posted on 2016-02-20, 18:57 authored by Hai Xiong, Frank SeelaHeterodimeric interstrand cross-linked DNA was constructed
by the
“bis-click” reaction carried out on preformed oligonucleotide
duplexes with the bis-azide 1. For this, alkynylated
8-aza-7-deazapurine or corresponding 5-substituted pyrimidine nucleosides
were synthesized. Cross-linking resulted in chemoselective formation
of heterodimeric duplexes while homodimers were suppressed. For product
identification, heterodimeric DNA was prepared by the “stepwise
click” reaction, while noncomplementary homodimers were accessible
by “bis-click” chemistry, unequivocally. Studies on
duplex melting of complementary cross-linked duplexes (heterodimers)
revealed significantly increased Tm values
compared to the non-cross-linked congeners. The stability of this
cross-linked DNA depends on the linker length and the site of modification.
Cross-linked homodimers hybridized with single-stranded complementary
oligonucleotides show much lower stability.