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“Bis‐Click” Ligation of DNA: Template‐Controlled Assembly, Circularisation and Functionalisation with Bifunctional and Trifunctional Azides
Author(s) -
Yang Haozhe,
Seela Frank
Publication year - 2017
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.201604857
Subject(s) - bifunctional , oligonucleotide , chemistry , click chemistry , combinatorial chemistry , chemical ligation , dna , ligation , solid phase synthesis , azide , nucleic acid , stereochemistry , organic chemistry , peptide , biochemistry , catalysis , microbiology and biotechnology , biology
Ligation and circularisation of oligonucleotides containing terminal triple bonds was performed with bifunctional or trifunctional azides. Both reactions are high yielding. Template‐assisted bis‐click ligation of two individual non‐complementary oligonucleotide strands was accomplished to yield heterodimers exclusively. In this context, the template fulfils two functions: it accelerates the ligation reaction and controls product assembly (heterodimer vs. homodimer formation). Intermolecular bis‐click circularisation of one oligonucleotide strand took place without template assistance. For construction of oligonucleotides with terminal triple bonds in the nucleobase side chain, 7‐ or 5‐functionalised 7‐deaza‐dA and dU residues were used. These oligonucleotides are directly accessible by solid‐phase synthesis. When trifunctional azides were employed instead of bifunctional linkers, functionalisation of the remaining azido group was performed with small molecules such as 1‐ethynyl pyrene, biotin propargyl amide or with ethynylated oligonucleotides. By this means, branched DNA was constructed.