A mild and efficient solid-support synthesis of novel oligonucleotide conjugates.
Conjugates of oligodeoxyribonucleotide phosphorothioate (ODN-PS) with folic acid, retinoic acid, arachidonic acid, and methoxypoly(ethylene glycol)propionic acid have been synthesized. The procedure involved the initial solid-phase preparation of 5'-amino-functionalized ODN-PS using N-pent-4-enoyl-derived (PNT) nucleoside phosphoramidites followed by conjugation of the oligonucleotide either to the ligand acids, using 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide as a coupling reagent, or to their corresponding succinimidyl derivatives. Subsequent exposure of the support to aqueous ammonium hydroxide (28%, 2 h, 55 degrees C) resulted in the release of the fully deprotected ODN conjugates, which were purified by reversed-phase HPLC or by preparative polyacrylamide gel electrophoresis. The identity of the oligonucleotide conjugates was confirmed by MALDI-TOF mass spectral analysis.
Habus
I
I
Hybridon, Inc., Cambridge, Massachusetts 02139, USA.
Xie
J
J
Iyer
R P
RP
Zhou
W Q
WQ
Shen
L X
LX
Agrawal
S
S
D064753:Ammonium Hydroxide; D000970:Antineoplastic Agents; D016718:Arachidonic Acid / Q000737:chemistry; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005492:Folic Acid / Q000737:chemistry; D006878:Hydroxides / Q000494:pharmacology; D013058:Mass Spectrometry; D015394:Molecular Structure; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011422:Propionates / Q000737:chemistry; D013053:Spectrophotometry; D013388:Succinimides / Q000737:chemistry; D013873:Thionucleotides / Q000737:chemistry; D014212:Tretinoin / Q000737:chemistry
D000970:Antineoplastic Agents; D006878:Hydroxides; D016376:Oligonucleotides, Antisense; D011422:Propionates; D013388:Succinimides; D013873:Thionucleotides; D016718:Arachidonic Acid; D011092:Polyethylene Glycols; D064753:Ammonium Hydroxide; D014212:Tretinoin; C028210:monomethoxypolyethylene glycol; D005492:Folic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; C029658:propionic acid