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Nucleic Acids Research, 1990, Vol. 18, No. 3 493-499
© 1990

CHEMISTRY

The synthesis of polyamide-oligonucleotide conjugate molecules

Jim Haralambidis*, Lucy Duncan, Karin Angus and Geoffrey W. Tregear

Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne Parkville, Victoria 3052, Australia

* To whom correspondence should be addressed

Received October 24, 1989. Accepted December 18, 1989.

We have developed methods for the synthesis of peptide-oligodeoxyribonucleotide conjugate molecules in particular, and polyamide-oligonucleotide conjugates in general. Synthesis is carried out by a solid-phase procedure and involves the assembly of a polyamide on the solid support, conversion of the terminal amino group to a protected primary aliphatic hydroxy group by reaction with {alpha},{omega}-hydroxycarboxylic acid derivatives, and finally oligonucleotide synthesis using phosphoramidite chemistry. The conjugate molecules can be used as DNA probes, with the polyamide component carrying one or more non-radioactive markers. These conjugates also have the potential to be used as anti-sense inhibitors of gene expression, with the peptide segment acting as a targeting moiety.


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