Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Aug 18;15(8):5692-707.
doi: 10.3390/molecules15085692.

Solid-phase synthesis of oligodeoxynucleotides containing N4-[2-(t-butyldisulfanyl)ethyl]-5-methylcytosine moieties

Sónia Pérez-Rentero  1 , Alejandra V Garibotti, Ramón Eritja
Affiliations

Solid-phase synthesis of oligodeoxynucleotides containing N4-[2-(t-butyldisulfanyl)ethyl]-5-methylcytosine moieties

Sónia Pérez-Rentero et al. Molecules. .

Abstract

An efficient route for the synthesis of the phosphoramidite derivative of 5-methylcytosine bearing a tert-butylsulfanyl group protected thiol is described. This building block is used for the preparation of oligonucleotides carrying a thiol group at the nucleobase at the internal position of a DNA sequence. The resulting thiolated oligonucleotides are useful intermediates to generate oligonucleotide conjugates carrying molecules of interest at internal positions of a DNA sequence.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1
Synthesis of the protected phosphoramidite derivative of 2’-deoxy-[2-(t-butyldisulfanyl)ethyl]-5-methylcytidine.
Scheme 2
Scheme 2
Products obtained after treatment of DMT-MeC(SStBu)-CPG (5) and DMT-C(SStBu)-CPG (6) with iodine or tert-butylhydroperoxide solutions. Reagents and conditions: (a) iodine or tert-butylhydroperoxide solution. (b) 3% trichloroacetic acid in dichloromethane. (c) concentrated ammonia, room temperature, 30 min.
Scheme 3
Scheme 3
Products obtained after treatment of DMT-CBzpMeC(SStBu)-CPG (11) and DMT-CBzpC(SStBu)-CPG (12) with iodine solution.
Scheme 4
Scheme 4
Potential products produced during the synthesis of oligonucleotides carrying N4- [2-(t-butyldisulfanyl)ethyl]-5-methylcytosine.
Figure 1
Figure 1
HPLC profiles of oligonucleotide 5’-d(TTCCAXATTACCG)-3’ after synthesis and after prolonged treatment of the support with tert-butylhydroperoxide solution for 6 and 12 h.
Scheme 5
Scheme 5
Synthesis of oligonucleotides carrying fluorescent molecules.
See this image and copyright information in PMC

References

    1. Beaucage S.L., Iyer R.P. The functionalization of oligonucleotide via phosphoramidite derivatives. Tetrahedron. 1993;49:1925–1963. doi: 10.1016/S0040-4020(01)86295-5. - DOI
    1. Connolly B.A. Chemical synthesis of oligonucleotides containing a free sulphydryl group and subsequent attachment of thiol specific probes. Nucleic Acids Res. 1985;13:4485–4502. doi: 10.1093/nar/13.12.4485. - DOI - PMC - PubMed
    1. Corey D.R. 48000-fold Acceleration of hybridization by chemically modified oligonucleotides. J. Am. Chem. Soc. 1995;117:9373–9374. doi: 10.1021/ja00141a038. - DOI
    1. Eritja R., Pons A., Escarceller M., Giralt E., Albericio F. Synthesis of defined peptide-oligonucleotide hybrids containing a nuclear transport signal sequence. Tetrahedron. 1991;47:4113–4120. doi: 10.1016/S0040-4020(01)86448-6. - DOI
    1. Zuckermann R.N., Schultz P.G. A hybrid sequence selective ribonuclease S. J. Am. Chem. Soc. 1988;110:6592–6594. doi: 10.1021/ja00227a066. - DOI

Publication types

MeSH terms

LinkOut - more resources