Nucleic Acids Research, 2003, Vol. 31, No. 14 4109-4118
© 2003 Oxford University Press
Biochemical properties of phosphonoacetate and thiophosphonoacetate oligodeoxyribonucleotides
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA and 1 Agilent Laboratories, 4380 Ziegler Road, Fort Collins, CO 80525, USA
*To whom correspondence should be addressed. Tel: +1 303 492 6095; Fax: +1 303 492 6194; Email: marvin.caruthers{at}colorado.edu
Phosphorus-modified phosphonoacetate and thiophosphonoacetate oligodeoxyribonucleotides were chemically synthesized and their biochemical properties evaluated. Under physiological pH, these DNA analogs possess negative charge and form stable, complementary A-like DNA:RNA heteroduplexes when analyzed via circular dichroism spectroscopy. Phosphonoacetate and thiophosphonoacetate oligomers were found to stimulate RNase H activity and to be completely resistant to degradation by snake venom phosphodiesterase, DNase I and HeLa cell nuclear extract. Further research has demonstrated that neutral, esterified forms of these analogs can be taken up by cells. Phosphonoacetate and thiophosphonoacetate oligomers therefore represent a new class of oligodeoxyribonucleotide analogs having phosphorus– carbon bonds with considerable potential for use in biological research.