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DNA with Branched Internal Side Chains: Synthesis of 5‐Tripropargylamine‐dU and Conjugation by an Azide‐Alkyne Double Click Reaction
Author(s) -
Sirivolu Venkata Ramana,
Chittepu Padmaja,
Seela Frank
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800313
Subject(s) - click chemistry , sonogashira coupling , oligonucleotide , chemistry , deoxyuridine , alkyne , combinatorial chemistry , propargyl bromide , phosphoramidite , propargyl , cycloaddition , side chain , covalent bond , conjugate , dna , azide , stereochemistry , organic chemistry , catalysis , biochemistry , palladium , mathematical analysis , polymer , mathematics
5‐Tripropargylamine‐2′‐deoxyuridine ( 1 a ) containing two terminal triple bonds was synthesized by a Pd‐assisted Sonogashira cross‐coupling reaction and was subsequently converted into the corresponding phosphoramidite building block ( 9 ) and employed in solid‐phase oligonucleotide synthesis. T m experiments demonstrate that the presence of covalently attached branched tripropargylamine residues has a positive effect on the base pair stability. The two terminal CC bonds of modified DNA were functionalized by means of Cu I ‐mediated 1,3‐dipolar cycloaddition reactions (click chemistry) with azides such as 3‐azido‐7‐hydroxycoumarin or 3′‐azido‐3′‐deoxythymidine (AZT) both in solution and on solid support. In particular, with the nonfluorescent 3‐azido‐7‐hydroxycoumarin a strongly fluorescent oligonucleotide bis‐dye conjugate was generated. For comparison, the N(3)‐propargylated 2′‐deoxyuridine 2 was prepared from 2′‐deoxyuridine and propargyl bromide and incorporated into DNA. The two terminal triple bonds of 1 a allow the simultaneous post‐modification of DNA by two reporter molecules and can be applied to almost any azido derivatives (oligonucleotides, proteins, polysaccharides etc.) including those forming dendrimeric side chains.