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Nucleic Acids Research, 1994, Vol. 22, No. 4 639-645
© 1994

CHEMISTRY

On the rapid deprotection of synthetic oligonucleotides and analogs

Nikolai N. Polushin, Alan M. Morocho, Ban-chin Chen and Jack S. Cohen

Cancer Pharmacology Section, Pharmacology Department Georgetown University Medical Center, Washington, DC 20007, USA

*To whom correspondence should be addressed

Received September 2, 1993. Accepted December 19, 1993.

The efficiency of ollgodeoxynucleotlde deprotection is greatly enhanced using a combination of: (a) ethanolamlne, and especially a mixture of hydrazine, ethanolamine and methanol, in place of the usual aqueous ammonia; (b) tert-butylphenoxyacetyl amino protecting groups, and (c) oxalyl link between the first nucleotlde and the polymeric support. The extent of base modification, particularly of C, is shown to be extremely low, and the quality of deprotected oligonucleotides is as high as In the case of ammonia deprotection. This method Is also shown to be applicable to the preparation of phosphorothloate and methylphosphonate oligodeoxynucleotldes and oligoribonucleotldes.


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