Biophysical and antisense properties of oligodeoxynucleotides containing 7-propynyl-, 7-iodo- and 7-cyano-7-deaza-2-amino-2'-deoxyadenosines.
The synthesis of 7-propynyl-, 7-iodo- and 7-cyano-7-deaza-2-amino-2'-deoxyadenosines is described. The nucleosides were synthesized, functionalized into the phosphoramidites and incorporated into oligodeoxynucleotides. Spectroscopic melting experiments against complementary RNA showed increases of 3-4 degreesC per modification for single substitutions and smaller increases per incorporation for multiple substitutions relative to unmodified control sequences. The 7-propyne and 7-iodo nucleosides were incorporated into antisense sequences targeting the 3'-UTR of murine C- raf mRNA. Both nucleosides demonstrated substitution-dependent potency. The sequences with three and four substitutions of the 7-propyne-7-deaza-2-amino-2'-deoxyadenosine exhibited a 2-3-fold increase in potency over unmodifed controls.
Balow
G
G
Department of Medicinal Chemistry and Antisense Biology, Isis Pharmaceuticals Inc., Carlsbad, CA 92008, USA.
Mohan
V
V
Lesnik
E A
EA
Johnston
J F
JF
Monia
B P
BP
Acevedo
O L
OL
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003839:Deoxyadenosines / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*
D003839:Deoxyadenosines; D016376:Oligonucleotides, Antisense