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Biomedical subjects

V V Vlassov

Publications and source records attributed to V V Vlassov.

At least 19 recordsLinked to original sources
PubMed1992

Affinity modification of human chromatin with reactive derivatives of oligonucleotides.

Reaction of 4-(N-2-chloroethyl-N-methylamino)benzylphosphamides of oligonucleotides (RCl-(pT)16 and RCl-(pApC)6) with human chromatin in intact nuclei and with metaphase chromosomes has been investigated. The oligonucleotides were targeted to poly(A) and poly(TG)-repeating DNA sequences. It was found that the reagents alkylate DNA and some proteins due to specific complex formation. The affinity character of the reaction was proved by the fact that free corresponding oligonucleotides taken in excess or preliminary treatment of chromatin with S1-nuclease both prevent the biopolymers from modification. The results obtained evidence that in human chromatin there are open DNA sequences available for affinity modification with oligonucleotide derivatives. Analysis of patterns of modified proteins within these chromatin areas may give a key to the structure of these chromatin sites.

Benzene Derivatives↗
PubMed1992

Interaction of cholesterol-conjugated alkylating oligonucleotide derivatives with cellular biopolymers.

Interactions of oligonucleotide derivatives with mammalian cells and cellular biopolymers have been investigated. The derivatives were oligonucleotides bearing an alkylating 2-chloroethylamino group at the 3'-end and a cholesterol residue at the 5'-terminal phosphate. These compounds are readily taken up by cells and react with cellular DNA, RNA and some proteins which may play a role in delivery of the compounds into cells.

Alkylation↗
PubMed1992

Cell membranes as barriers for antisense constructions.

The results of studies on interaction of oligonucleotides and polynucleotides with cell membranes are reviewed. Oligonucleotides and polynucleotides bind to lipid membranes in the presence of divalent cations that may result in spontaneous encapsulation of nucleic acids and transfer of the formed vesicles to the other side of the membrane. Oligonucleotides can enter eukaryotic cells and interact with cellular RNA and DNA. On the surface of eukaryotic cells, there are proteins capable of binding to nucleic acids that may be involved in oligonucleotide uptake. Oligonucleotides bind to cellular CD4 receptors. Efficient delivery into cells can be achieved by conjugation of oligonucleotides to lipophilic groups or by encapsulation into membrane carriers.

Animals↗
PubMed1992

Sequence-specific cleavage of single-stranded DNA by oligonucleotides conjugated to bleomycin.

Cleavage of a single-stranded DNA fragment by complementary oligonucleotides conjugated to bleomycin A5 has been investigated. The conjugates efficiently cleave the DNA at the GT sequences near the oligonucleotide binding site. The temperature dependence of the reaction and the composition of the degradation products indicate that the oligonucleotide-linked bleomycin attacks the available double-stranded DNA regions within the oligonucleotide-DNA duplex and in the hairpin DNA region in the vicinity of the carrier oligonucleotide binding site.

Antibiotics, Antineoplastic↗
PubMed1991

Reactive oligonucleotide derivatives as gene-targeted biologically active compounds and affinity probes.

Development of efficient methods for synthesis of oligonucleotides and oligonucleotide analogs has opened up the possibility of designing a broad spectrum of affinity reagents for specific modification of nucleic acids and proteins. These affinity reagents are used for investigation of the topology of ribosomes and nucleic acid polymerases. Oligonucleotides and their analogs are already used for suppression of specific gene expression and for elucidation of the physiological role of their products. Oligonucleotide derivatives appear to offer considerable promise as potential gene-targeted drugs such as antivirals and specific inhibitors of oncogene expression.

Affinity Labels↗
PubMed1991

Sequence-specific alkylation of dsDNA with derivatives of pyrimidine oligonucleotides conjugated to 2-chloroethylamine groups.

Reaction of homopyrimidine oligonucleotides bearing a 5'-terminal alkylating aromatic 2-chloroethyl-amino group with a bovine papilloma vector expressing human interferon-gamma was investigated. The oligonucleotide derivatives bound to corresponding homopurine-homopyrimidine sequences in dsDNA and alkylated guanosine residues at these sites in the purine strand of the target. The alkylated DNA can be cleaved at the modified residues. At pH 5.4, the reaction was highly specific to the target sequences; at pH less than 5, some nonspecific reactions were observed at the sequences partially complementary to the oligonucleotides. Elongation of the linker between the alkylating group and the oligonucleotide phosphate increased the alkylation efficiency. Repeated treatment of the DNA with gradually increased concentrations of the reagent resulted in quantitative modification of the target guanosines.

Alkylation↗
PubMed1990

Sequence-specific chemical modification of chromatin DNA with reactive derivatives of oligonucleotides.

Chemical modification of the chromatin DNA with alkylating derivatives of oligothymidylate (pT)16 and oligoadenylate (pA)16 bearing 4-(N-2-chloroethyl-N-methylamino)benzylphosphamide group at the 5'-phosphate has been investigated. It was found that the derivatives do react with DNA in chromatin. The reactions occur presumably at the complementary sequences of the DNA since the reaction of the oligothymidylate derivative is inhibited by oligonucleotide (pT)16 taken in excess and is not influenced by hexadecanucleotide of a random structure. Isolated DNA does not react with the oligothymidylate derivative. It is concluded that in chromatin, DNA is partially unwound or possesses some sites which can be opened easily in the presence of complementary oligonucleotides.

Alkylating Agents↗
PubMed1990

Antisense oligonucleotide derivatives as gene-targeted drugs.

The strategies and problems involved in designing oligonucleotide derivatives as gene-targeted drugs are discussed. Experiments with isolated and cellular nucleic acids, studies with infected cell cultures, and preliminary animal tests all demonstrate that various derivatives of complementary oligonucleotides (antisense oligonucleotide derivatives) can act as extremely specific and potent inhibitors of gene expression. The design and synthesis of more stable oligonucleotide analogues that can enter mammalian cells and efficiently affect preselected nucleic acids will result in the development of a new generation of drugs, including those with antiviral and anticancer properties.

Animals↗
PubMed1989

Synthesis of alkylating oligonucleotide derivatives containing cholesterol or phenazinium residues at their 3'-terminus and their interaction with DNA within mammalian cells.

5'-[32P]-labelled alkylating decathymidylate [4-(N-2-chloroethyl)N-methylaminobenzyl]-5'-phosphamide derivatives containing cholesterol or phenazinium residues at their 3'-termini were synthesized and used for alkylation of DNA within mammalian cells. The uptake of the cholesterol derivative by the cells and the extent of DNA alkylation are about two orders of magnitude higher than those of a similar alkylating derivative lacking the groups at the 3'-termini. The presence of the phenazinium residue at the 3'-terminus of the oligonucleotide reagent does not improve the reagent uptake by the cells but drastically increases the DNA modification efficiency.

Alkylating Agents↗