[Oligo(2'-O-Methylribonucleotides) and their derivatives: IV. Conjugates of oligo(2'-O-methylribonucleotides) with minor groove binders and intercalators: synthesis, properties and application].

Conjugates of pyrimidine triplex forming 3'-protected oligo(2'-O-methylribonucleotides) with minor groove binders (MGB) and triplex specific intercalator benzoindoloquinoline (BIQ) at 5'-terminus were synthesized. The conjugates formed stable complexes with target dsDNA by simultaneous binding both in its minor and major grooves and BIQ intercalation. The dissociation constants and thermal stability of the conjugate complexes with model dsDNA corresponding to polypurine tract (PPT) of genes nef and pol from HIV proviral genome were determined.

[Effect of structural factors on the stability of duplexes formed by oligonucleotide conjugates with minor groove ligands].

The effect of structural factors on the stability of duplexes formed by DNA minor groove binders conjugated with oligonucleotide mono- or diphosphoramidates of the general formula Oligo-MGBm (where Oligo is an oligonucleotide; m = 1 or 2; MGB is -L(Py)2R, L(Py)4R, -L(Im)4R, or -L(Py)4NH(CH2)3CO(Py)4R; Py is a 4-aminopyrrol-2-carboxylic acid residue, L is a gamma-aminobutyric acid or an epsilon-aminocaproic acid residue, R = OEt, NH(CH2)6NEt2, or NH(CH2)6N+Me3) was studied by the method of thermal denaturation. The mode of binder interaction with minor groove depends on the conjugate structure; it may be of the parallel head to head type for bisphosphoramidates and of the antiparallel head to tail type for monophosphoramidates of a hair-pin structure. The effects of the duplexes with parallel orientation (bisphosphoramidates, MGB is L(Py)4R, m = 2) and those of the hairpin structure with the antiparallel orientation (monophosphoramidates, MGB is L(Py)4(CH2)3CO(Py)4R, m = 1) on Tm values were close.

[Stabilization of G x C-containing DNA duplexes by polyamides with parallel orientation in the minor groove].

The polyamides based on 4-amino-1-methylpyrrol-2-carboxylic acid, 4-amino-1-methylimidazole-2-carboxylic acid, and beta-alanine that stabilize oligonucleotide duplexes consisting of G x C pairs through parallel packing in the minor groove were studied. The initial duplex TTGCGCp x GCGCAA melts at 28 degrees C; the TTGCGCp[NH(CH2)3COPyIm betaImNH(CH2)3NH(CH3)2][NH(CH2)3COIm betaImPyNH(CH2)3N(CH3)2] x GCGCAA duplex (bisphosphoramidate with parallel orientation of ligands, where Py, Im, and beta are the residues of 1-methyl-4-aminopyrrol-2-carboxylic and 1-methyl-4-aminoimidazole-2-carboxylic acids and beta-alanine, respectively), at 48 degrees C; and the TTGCGCp[NH(CH2)3COIm betaImPyNH(CH2)3COIm betaImPyNH(CH2)3N(CH3)2] x GCGCAA duplex (a hairpin structure with antiparallel orientation), at 56 degrees C. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol.

[Functionalization of oligonucleotides containing internucleotide phosphoamide bonds].

A new method for functionalization of oligonucleotides by addition of aminoalkyl derivatives to the intermolecular phosphorus atom of the oligonucleotide N3'-P5' phosphoramidate bond in the presence of triphenylphosphine, 4-dimethylaminopyridine, and 2,2'-dipyridyl disulfide was suggested. The reaction proceeded with both low-molecular alkylamines (1,6-diaminohexane or N,N-dimethyl-1,3-diaminopropane) and a ligand in minor groove containing a aminoalkyl group.

[Stabilization of DNA triple helix using conjugates of oligonucleotides and synthetic ligands].

Possibility of stabilization of DNA triple helix is discussed using a covalent conjugation to the third strand (through its terminal phosphate) of ligands that have affinity to double and triple helices. Two types of stabilizers are considered: minor groove binders based on oligopyrroles and triplex-specific interacalators. As a target, a synthetic 29-mer duplex containing a natural polypurinic sequence of the human immunodeficiency provirus was employed.