Synthesis of azidoaniline derivatives of oligonucleotides and investigation of their photochemical behavior.

Abstract

A series of aryl azides, p-N3C6H4NH(CH2)nNH2 with n = 2-6, have been synthesized and used to prepare oligonucleotide derivatives carrying photoreactive the p-azidoaniline residue. Reactive moieties have been coupled to the 5'-terminal phosphate of d(pGATACCAA) [compounds IV(b), IV(c), and IV(e) with n = 3, 4, and 6, respectively] and of d(pGCC) [compound V(b) with n = 3] via a phosphoamide bond. Irradiation at wavelengths over > 300 nm of IV(b) and V(b) (n = 3) resulted in cleavage of the P-N bond. However, under the same reaction conditions, the P-N bond remained intact for compounds containing longer spacers [IV(c) and IV(e)]. Intraduplex reaction of the latter derivatives with d(GGTATCp)NH(CH2)6NH2 resulted in cross-linking dependent on the presence of an aliphatic amino group. The results obtained have demonstrated that the azidoaniline derivatives of oligonucleotides capable of the affinity modification of a specific target can be prepared. However, the sufficiently long aliphatic spacer group is necessary to prevent P-N bond cleavage within the photoreactive oligonucleotide.