Solid phase synthesis of a metronidazole oligonucleotide conjugate

Abstract

Direct, solid phase synthesis of an oligonucleotide conjugate of the antibiotic drug metronidazole was accomplished by the phosphoramidite method. Removal of protecting groups and cleavage from the controlled pore glass (CPG) solid support was successful using mild conditions (20% Et(3)N in pyridine, then conc. NH(3) (aq) at rt for 30 min) whereas standard conditions (conc. NH(3) (aq) at 55 degrees C for 16 h) cleaved the drug.

Scheme 1

Figure 1

Reversed phase HPLC profiles of the target metronidazole oligonucleotide conjugate 5 with retention time 13.1 min (upper trace), aminoethyl oligonucleotide conjugate 4 with retention time 11.7 min (middle trace) and a co-injection of both conjugates 4 and 5 (lower trace). The vertical axes show milliabsorbance units (mAU) and the horizontal axes show retention time.