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Synthesis and Hybridization Properties of Oligonucleotides Containing Polyamines at the C‐2 Position of Purines: A Pre‐synthetic Approach for the Incorporation of Spermine into Oligodeoxynucleotides Containing 2‐(4,9,13‐Triazatridecyl)‐2′‐deoxyguanosine
Author(s) -
Potier Pierre,
Abdennaji Adib,
Behr JeanPaul
Publication year - 2000
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 - 10.1002/1521-3765(20001117)6:22<4188::aid-chem4188>3.0.co;2-n
Subject(s) - spermine , synthon , phosphoramidite , oligonucleotide , stereochemistry , polyamine , thymine , dna , nucleobase , chemistry , spermidine , biochemistry , enzyme
We have developed a synthesis of spermine‐containing oligonucleotides (ODN‐sper) which allows incorporation of multiple polyamine residues. This approach was based on the per‐trifluoroacetylated 5′DMT‐dGsper phosphoramidite synthon. Its coupling yield with resin‐bound ODN decreased dramatically when close to the 3′‐end. Optimization of the coupling conditions allowed 22‐mer ODNs containing up to six spermine residues to be synthesized. Several ODNs of different sequences with 1–4 pendent spermines could be purified and their hybridization properties were evaluated. Duplex melting temperatures increased linearly with the number of polyamine residues (Δ T m /sper=3.0±0.2 °C in 100 m M NaCl). This compares very favorably with values reported for duplexes of similar initial stability containing other cation‐substituted bases. Moreover, the stability increase was neither sequence nor position‐dependent, and even contiguous spermine residues did not cross‐talk. Extrapolation based on these findings leads to the conclusion that a duplex formed with a 22‐mer oligonucleotide containing seven spermine residues would be as stable as genomic DNA, which highlights its potential for DNA strand invasion.