A convenient solid-phase method for the synthesis of novel oligonucleotide-folate conjugates.

We describe the preparation of two batches of a polymer support for the incorporation of folic acid into oligonucleotides. The method permits the regioselective attachment of a target nucleic acid sequence through its 3'-end to either the alpha-or gamma-carboxyl group of L-glutamic acid, respectively. The supports have been tested in solid-phase synthesis of oligonucleotide-folate conjugates for cell delivery studies.

Incorporation of side-chain groups of basic amino acids into oligonucleotides via the 2'-position of uridine.

Certain amino acids and short peptides are known to act as enhancers of ribozyme-mediated RNA cleavage at low concentration of magnesium ion. Thus, covalent conjugates of oligonucleotides and some amino acids may have a potential for development as sequence-specific artificial ribonucleases. Here we would like to report an incorporation of basic amino acids, lysine and histidine, into oligonucleotides at the 2'-position of a uridine residue.

Oligonucleotides with 2'-O-carboxymethyl group: synthesis and 2'-conjugation via amide bond formation on solid phase.

An efficient method for synthesis of oligonucleotide 2'-conjugates via amide bond formation on solid phase is described. Protected oligonucleotides containing a 2'-O-carboxymethyl group were obtained by use of a novel uridine 3'phosphoramidite, where the carboxylic acid moiety was introduced as its allyl ester. This protecting group is stable to the conditions used in solid-phase oligonucleotide assembly, but easily removed by Pd(0) and morpholine treatment.

Synthesis of oligonucleotide 2'-conjugates via amide bond formation in solution.

An efficient method for synthesis of 2'-O-carboxymethyl oligonucleotides is described. Fully deprotected oligonucleotides containing a carboxymethyl group at the 2'-position of sugar residue were obtained by a two-step procedure by periodate cleavage of an oligonucleotide containing 1,2-diol group followed by oxidation of the 2'-aldehyde resulted with sodium chlorite. 2'-O-Carboxymethyl oligonucleotides prepared were efficiently coupled in aqueous solution in the presence of a water-soluble carbodiimide to a number of amino acid derivatives or short peptides to afford novel 2'-conjugates of high purity in good yield.