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The preparation of two novel 2′-O-alkyl phosphoramidites bearing 1,2-diol and hydrazide functions for a chemoselective ligation is described. The former amidite was used to obtain 2′-modified oligodeoxyribonucleotides, which can be later oxidised by NaIO4 to generate 2′-aldehyde oligonucleotides. These were successfully conjugated to acceptor molecules. The latter amidite also showed good coupling yields, but the hydrazide function was demonstrated to be labile under basic deprotection conditions. [ABSTRACT FROM AUTHOR]

Abstract: Oligodeoxyribonucleotides that contain a novel nucleoside, 2′-O-(2-hydrazinoethyl)uridine, were synthesised by NaBH3CN reduction of hydrazones formed from 2′-O-(2-oxoethyl)oligonucleotides with FmocNHNH2, followed by concd aq NH3 deprotection. The 2′-hydrazine oligonucleotides obtained were then used to synthesise a number of conjugates with aldehydes via hydrazone formation and with1,3-diketones via pyrazole formation. The method was shown to be applicable for the preparation of oligonucleotide–peptide conjugates. [Copyright &y& Elsevier]

Abstract: 2′-O-[2-(2,3-Diacetoxypropyl)amino-2-oxoethyl]uridine 3′-phosphoramidite was prepared and used in solid-phase synthesis to obtain oligonucleotides containing a 1,2-diol group, which may then be converted into a 2′-aldehyde group. The oligonucleotides were conjugated efficiently to various molecules by chemoselective ligation that involves an addition–elimination reaction between the 2′-aldehyde group and a suitable nucleophile, such as a hydrazine, a O-alkylhydroxylamine or an 1,2-aminothiol. The method was applied successfully to the conjugation of peptides to oligonucleotides at the 2′-position. [Copyright &y& Elsevier]

Abstract: Oligodeoxyribonucleotides were synthesized that contain a novel nucleoside, 2′-O-(2,3-dihydroxypropyl)cytidine. Its 2′-diol group was blocked by an allyloxycarbonyl protecting group. Selective deprotection of diol group(s) of the support-immobilized blocked oligodeoxyribonucleotide by Pd(0) followed by periodate oxidation resulted in generation of the 2′-aldehyde group(s) on solid-phase. The modified oligonucleotides were used to prepare a number of conjugates with acridine, biotin and N-modified laminin peptides by oxime, hydrazone and hydrazine formation. The method may be applicable to the synthesis of oligonucleotide–peptide conjugates. [Copyright &y& Elsevier]