Abstract: A double- or single-stranded oligonucleotide comprising one or more respectively inter- or intra-oligonucleotide covalent cross-linkages, wherein the or each covalent linkage consists of an amide bond between a primary amine group of one strand and a carboxyl group of the other strand or the same strand, respectively, said primary amine group being directly substituted in the 2′ position of the strand nucleotide monosaccharide ring, and said carboxyl group being carried by an aliphatic spacer group substituted on a nucleotide or nucleotide analog of the other strand or the same strand, respectively. A method for preparing such oligonucleotides, and nucleotide or non-nucleotide synthons useful for preparing an oligonucleotide of the above kind, are also disclosed.