By the reaction of poly(acryloyl chloride) with N-(3-aminopropyl)imidazole, poly(N-(3-(1H-imidazol-1-yl)propyl)acrylamide) was synthesized. The new polymer contains an imidazole ring removed from the main chain by a s...By the reaction of poly(acryloyl chloride) with N-(3-aminopropyl)imidazole, poly(N-(3-(1H-imidazol-1-yl)propyl)acrylamide) was synthesized. The new polymer contains an imidazole ring removed from the main chain by a spacer of five bonds. The structure and purity, molecular weight, hydrodynamic and thermosensitive properties of the obtained sample were studied by1H-and13C-NMR, FTIR spectroscopy, acid-base titration, light scattering, turbidimetry and viscometry. The observed ability of the imidazole-containing polymer to form and destroy associates in water-salt solutions at pH 6.6-7.4 and temperatures of 29-48℃ indicates that these are promising candidates for designing complex biomedical systems. The new polymer is able to form complexes with oligo-DNA more actively than poly(1-vinylimidazole), which is of interest for gene delivery applications. The polymer cross-linked with epichlorohydrin gives micro-relief coatings on the plastic surface, and the modified surface is able to attach negatively charged objects. This thermo-and pH-sensitive polymer modification can be applied to create finely controlled surfaces for cell culturing.展开更多
Polymeric amines are being studied intensively as components of systems for gene delivery in genetic engineering and gene therapy of genetic disorders, including cancer. Despite remarkable achievements in the field, p...Polymeric amines are being studied intensively as components of systems for gene delivery in genetic engineering and gene therapy of genetic disorders, including cancer. Despite remarkable achievements in the field, polymeric amines, such as polyethyleneimine, show some disadvantages. Strong interaction between the amine-containing polymer and nucleic acid hampers the release of nucleic acid in the cell cytoplasm. Amine groups can interact with the cell membrane which results in cell death. These limitations of polymeric amines stimulated an investigation of new structures for gene delivery. Imidazole-containing polymers have attracted attention as lesser basic substances, while they are able to interact with polymeric acids. Further development of imidazole-based gene delivery agents requires knowledge about some fundamental aspects of interaction between nucleic acids, and polymeric imidazoles. In this work, we studied the complexation of poly(1-vinylimidazole) and oligomeric DNA. We found that the number of active sites capable of binding with negatively charged phosphate groups is comparable with the number of protonated imidazole units in the case of high molecular weight polymer. The increase in polymer charge by 1-bromopropane quaternizating 1%?5% imidazole units or by decreasing the pH to 6.5?7 considerably increased the ability of poly(1-vinylimidazole) to interact with oligonucleotides. The pH sensitivity of this interaction is interesting for cancer gene therapy because the tumours have a lowered intercellular pH (stable oligonucleotide complex) and a higher extracellular pH which can lead to complex dissociation. Minimal critical length for complexation of quaternized poly(1-vinylimidazole) and DNA is below eight units which corresponds to polymers with amine groups. Fluorescence-tagged poly(1-vinylimidazole) samples were obtained and their potential for monitoring the polymer and polymer-oligonucleotide complex internalization into living cells was demonstrated.展开更多
The siliceous frustules of diatom algae contain complex proteins known as silaffins, which consist of a peptide chain with grafted polyamine chains. These polyamines contain twenty or more nitrogen atoms with trimethy...The siliceous frustules of diatom algae contain complex proteins known as silaffins, which consist of a peptide chain with grafted polyamine chains. These polyamines contain twenty or more nitrogen atoms with trimethylene groups between the nitrogens. We synthesized a set of polymers containing grafted long-chain polyamine fragments by using acryloyl chloride （ACh） polymers and activated acrylic acid copolymers as the starting materials. The new polymers contained 0.05 mol%-3.2 mol% of polyamine chains, which corresponded to 0.06-3.56 mmol·g- 1 amine groups. The new amine-containing polymers formed complexes with short （19-21-mer） deoxyribonucleic acid （DNA） and ribonucleic acid （RNA） strands, and these complexes penetrated into model yeast cells and A549 lung cancer cell. This study demonstrates the potential of these species based on long-chain polyamines to serve as novel gene delivery systems.展开更多
基金supported by the Russian Science Foundation(No.22-24-00474).
文摘By the reaction of poly(acryloyl chloride) with N-(3-aminopropyl)imidazole, poly(N-(3-(1H-imidazol-1-yl)propyl)acrylamide) was synthesized. The new polymer contains an imidazole ring removed from the main chain by a spacer of five bonds. The structure and purity, molecular weight, hydrodynamic and thermosensitive properties of the obtained sample were studied by1H-and13C-NMR, FTIR spectroscopy, acid-base titration, light scattering, turbidimetry and viscometry. The observed ability of the imidazole-containing polymer to form and destroy associates in water-salt solutions at pH 6.6-7.4 and temperatures of 29-48℃ indicates that these are promising candidates for designing complex biomedical systems. The new polymer is able to form complexes with oligo-DNA more actively than poly(1-vinylimidazole), which is of interest for gene delivery applications. The polymer cross-linked with epichlorohydrin gives micro-relief coatings on the plastic surface, and the modified surface is able to attach negatively charged objects. This thermo-and pH-sensitive polymer modification can be applied to create finely controlled surfaces for cell culturing.
基金financial support from a joint grant of the Russian Science Foundation (16-45-02001)the Department of Science Technology of the Ministry of Science and Technology of the Republic of India (INT/RUS/RSF/10)
文摘Polymeric amines are being studied intensively as components of systems for gene delivery in genetic engineering and gene therapy of genetic disorders, including cancer. Despite remarkable achievements in the field, polymeric amines, such as polyethyleneimine, show some disadvantages. Strong interaction between the amine-containing polymer and nucleic acid hampers the release of nucleic acid in the cell cytoplasm. Amine groups can interact with the cell membrane which results in cell death. These limitations of polymeric amines stimulated an investigation of new structures for gene delivery. Imidazole-containing polymers have attracted attention as lesser basic substances, while they are able to interact with polymeric acids. Further development of imidazole-based gene delivery agents requires knowledge about some fundamental aspects of interaction between nucleic acids, and polymeric imidazoles. In this work, we studied the complexation of poly(1-vinylimidazole) and oligomeric DNA. We found that the number of active sites capable of binding with negatively charged phosphate groups is comparable with the number of protonated imidazole units in the case of high molecular weight polymer. The increase in polymer charge by 1-bromopropane quaternizating 1%?5% imidazole units or by decreasing the pH to 6.5?7 considerably increased the ability of poly(1-vinylimidazole) to interact with oligonucleotides. The pH sensitivity of this interaction is interesting for cancer gene therapy because the tumours have a lowered intercellular pH (stable oligonucleotide complex) and a higher extracellular pH which can lead to complex dissociation. Minimal critical length for complexation of quaternized poly(1-vinylimidazole) and DNA is below eight units which corresponds to polymers with amine groups. Fluorescence-tagged poly(1-vinylimidazole) samples were obtained and their potential for monitoring the polymer and polymer-oligonucleotide complex internalization into living cells was demonstrated.
基金financial support from a joint grant of the Russian Science Foundation(#6-45-02001)the Department of Science Technology of the Ministry of Science and Technology of the Republic of India(#INT/RUS/RSF/10)
文摘The siliceous frustules of diatom algae contain complex proteins known as silaffins, which consist of a peptide chain with grafted polyamine chains. These polyamines contain twenty or more nitrogen atoms with trimethylene groups between the nitrogens. We synthesized a set of polymers containing grafted long-chain polyamine fragments by using acryloyl chloride （ACh） polymers and activated acrylic acid copolymers as the starting materials. The new polymers contained 0.05 mol%-3.2 mol% of polyamine chains, which corresponded to 0.06-3.56 mmol·g- 1 amine groups. The new amine-containing polymers formed complexes with short （19-21-mer） deoxyribonucleic acid （DNA） and ribonucleic acid （RNA） strands, and these complexes penetrated into model yeast cells and A549 lung cancer cell. This study demonstrates the potential of these species based on long-chain polyamines to serve as novel gene delivery systems.
