Pavel Chelushkin - Academia.edu (original) (raw)
Papers by Pavel Chelushkin
2022 International Conference Laser Optics (ICLO), Jun 20, 2022
European Polymer Journal, 2017
A practical protocol has been designed to synthesize dendronized polymeric chelating agents conta... more A practical protocol has been designed to synthesize dendronized polymeric chelating agents containing 1,4,7,10-tetraazacyclodocecane-N,N',N'',N‴-tetraacetic acid (DOTA) ligand. The efficiency of suggested approach was verified by grafting of N-vinylpyrrolidone-acrolein P(VP-Ac) copolymer with dendrons containing several DOTA residues as compared to acylation of Nvinylpyrrolidone-vinylamine P(VP-VA) copolymer with active ester of DOTA. It was shown that attachment of pre-synthesized branched building blocks using hydrazone ligation strategy is an efficient method to increase the payload of carrier molecule. A similar methodology was applied for the preparation of polymer grafted by dendrons bearing DOTA complexes with paramagnetic ions (Gd 3+ and Mn 2+). Obtained results evidenced that polymer-metal complexes possess high relaxivity values and can be considered as promising candidates for MRI contrast agents. The presented results demonstrate utility of hydrazone ligation strategy for the synthesis and screening of dendronized polymeric carriers of different nature.
Polymers
Despite the fact that amphiphilic block copolymers have been studied in detail by various methods... more Despite the fact that amphiphilic block copolymers have been studied in detail by various methods both in common solvents and aqueous dispersions, their hydrodynamic description is still incomplete. In this paper, we present a detailed hydrodynamic study of six commercial diblock copolymers featuring the same hydrophilic block (poly(ethylene glycol), PEG; degree of polymerization is ca. 110 ± 25) and the following hydrophobic blocks: polystyrene, PS35-b-PEG115; poly(methyl methacrylate), PMMA55-b-PEG95; poly(1,4-butadyene), PBd90-b-PEG130; polyethylene PE40-b-PEG85; poly(dimethylsiloxane), PDMS15-b-PEG115; and poly(ɛ-caprolactone), PCL45-b-PEG115. The hydrodynamic properties of block copolymers are investigated in both an organic solvent (tetrahydrofuran) and in water micellar dispersions by the combination of static/dynamic light scattering, viscometry, and analytical ultracentrifugation. All the micellar dispersions demonstrate bimodal particle distributions: small compact (hydrod...
![Research paper thumbnail of Aggregation-Induced Ignition of Near-Infrared Phosphorescence of Non-Symmetric [Pt(C^N*N’^C’)] Complex in Poly(caprolactone)-based Block Copolymer Micelles: Evaluating the Alternative Design of Near-Infrared Oxygen Biosensors](https://attachments.academia-assets.com/92955032/thumbnails/1.jpg)
](Biosensors
In the present work, we described the preparation and characterization of the micelles based on a... more In the present work, we described the preparation and characterization of the micelles based on amphiphilic poly(ε-caprolactone-block-ethylene glycol) block copolymer (PCL-b-PEG) loaded with non-symmetric [Pt(C^N*N’^C’)] complex (Pt1) (where C^N*N’^C’: 6-(phenyl(6-(thiophene-2-yl)pyridin-2-yl)amino)-2-(tyophene-2-yl)nicotinate). The obtained nanospecies displayed the ignition of near-infrared (NIR) phosphorescence upon an increase in the content of the platinum complexes in the micelles, which acted as the major emission component at 12 wt.% of Pt1. Emergence of the NIR band at 780 nm was also accompanied by a 3-fold growth of the quantum yield and an increase in the two-photon absorption cross-section that reached the value of 450 GM. Both effects are believed to be the result of progressive platinum complex aggregation inside hydrophobic poly(caprolactone) cores of block copolymer micelles, which has been ascribed to aggregation induced emission (AIE). The resulting phosphorescent...
Chemical Communications, 2022
Covalent conjugation of human serum albumin with pH-sensitive fluorescein and an Ir(iii) phosphor... more Covalent conjugation of human serum albumin with pH-sensitive fluorescein and an Ir(iii) phosphorescent complex affords a biocompatible lifetime-based dual sensor.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
The topic is the chemistry of coinage metals, and this is, in fact, a very old story (Fig. 10.1).... more The topic is the chemistry of coinage metals, and this is, in fact, a very old story (Fig. 10.1). The chemistry of coinage metals started thousand years ago with the production of pure metals, and the metals copper, silver and gold were used to cast coins.
Journal of peptide science : an official publication of the European Peptide Society, 2017
Oxime ligation is a powerful tool in various bioconjugation strategies. Nevertheless, high reacti... more Oxime ligation is a powerful tool in various bioconjugation strategies. Nevertheless, high reaction rates and quantitative yields are typically reported for aldehyde-derived compounds. In contrary, keto groups react much slower, with quantitative yields achieved at 5 h for low-molecular weight compounds and more than 15 h for polymers or dendrimers. In this communication, we report that oxime ligation proceeds rapidly with quantitative (>95%) conversion within 1.5-2 h in pure acetic acid. The practical utility of suggested technique is illustrated by the synthesis of peptide-steroid and peptide-polymer conjugates of model aminooxy-peptides. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Bioconjugate Chemistry, 2016
Molecular Pharmaceutics, 2016
Journal of Photochemistry and Photobiology A: Chemistry, 2017
Abstract The development of organelle-specific phosphorescent multiphoton probes is a rapidly gro... more Abstract The development of organelle-specific phosphorescent multiphoton probes is a rapidly growing area in biomedical imaging. Phosphorescent properties allow spectral or time-resolved discrimination from autofluorescence, while the use of two-photon microscopy provides higher spatial resolution as well as deeper penetration into the sample compared to conventional microscopies. The main challenge in this area is the design of probes that combine a complex of desired properties. Here we present investigation of the phosphorescent homoleptic alkynyl gold(I) cluster, (AuC 2 R) 10 (R − 2,6-dimethyl-4-heptanol), which combines nonlinear optical properties with selectivity to lipid droplets of adipocytes and other cells. This label reveals high two-photon absorption and emission cross-sections in hexane, good solubility in triglycerides (vegetable oil) and microsecond lifetimes both in solution and in biological tissues. These features make it a promising probe for multiphoton bioimaging as demonstrated by successful visualization of various adipose tissues (subcutaneous fat, visceral adipose tissue, adipose tissue of mesentery) of different animals (pigeon, chicken, mouse) as well as lipid droplets in Hep G2 cells. The complex demonstrates high selectivity to lipid droplets in animal tissues and cells. The probe lifetimes in microsecond domain made possible its visualization using phosphorescent lifetime imaging (PLIM) techniques.
Contrast Media & Molecular Imaging, 2015
Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis ... more Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T 1 relaxivity (6.5 mM À1 s À1 at 7 T) than the commercial agent Magnevist® (3.4 mM À1 s À1). Cellular uptake of Cx43-specific T 1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI.
Bioorganiceskaâ himiâ
A set of GnRH analogues containing nuclear localization signal (NLS) of SV-40 virus large T-antig... more A set of GnRH analogues containing nuclear localization signal (NLS) of SV-40 virus large T-antigen have been synthesized using solid phase peptide synthesis and chemical ligation technique. Selective chemical ligation was achieved as a result of hydrazone formation in the course of interaction between NLS hydrazide and GnRH analog modified by pyruvic acid. The efficiency of synthesized peptide carriers was demonstrated in experiments with human cancer cells transfected by reporter luciferase and beta-galactosidase genes or suicide HSV-1 thymidine kinase gene. It was shown that selectivity of action on cancer cells can be achieved as a result of peptide/DNA complex penetration through the cell membrane by GnRH receptor-mediated endocytosis pathway.
Using the methods of potentiometry, UV spectroscopy, and static and dynamic light scattering, the... more Using the methods of potentiometry, UV spectroscopy, and static and dynamic light scattering, the interaction of micelles of a cationic amphiphilic diblock copolymer with an oppositely charged linear homopolyelectrolyte in dilute aqueous solutions is studied. The copolymer is represented by polystyrene-block-poly(N-ethyl-4-vinylpyridinium bromide); the polyelectrolyte, by poly(methacrylic acid), and its sodium salt, sodium poly(methacrylate). As is shown, polystyrene-block-poly(N-ethyl-4-vinylpyridinium bromide) in water forms spherical micelles with the core composed of insoluble polystyrene units and the corona composed of cationic blocks of poly(N-ethyl-4-vinylpyridinium bromide); the average aggregation number is about 40. The addition of poly(methacrylic acid) or sodium polymethacrylate is accompanied by cooperative electrostatic binding of oppositely charged units, which leads to the formation of interpolyelectrolyte complexes. Depending on the charge ratio in the solution, ei...
2022 International Conference Laser Optics (ICLO), Jun 20, 2022
European Polymer Journal, 2017
A practical protocol has been designed to synthesize dendronized polymeric chelating agents conta... more A practical protocol has been designed to synthesize dendronized polymeric chelating agents containing 1,4,7,10-tetraazacyclodocecane-N,N',N'',N‴-tetraacetic acid (DOTA) ligand. The efficiency of suggested approach was verified by grafting of N-vinylpyrrolidone-acrolein P(VP-Ac) copolymer with dendrons containing several DOTA residues as compared to acylation of Nvinylpyrrolidone-vinylamine P(VP-VA) copolymer with active ester of DOTA. It was shown that attachment of pre-synthesized branched building blocks using hydrazone ligation strategy is an efficient method to increase the payload of carrier molecule. A similar methodology was applied for the preparation of polymer grafted by dendrons bearing DOTA complexes with paramagnetic ions (Gd 3+ and Mn 2+). Obtained results evidenced that polymer-metal complexes possess high relaxivity values and can be considered as promising candidates for MRI contrast agents. The presented results demonstrate utility of hydrazone ligation strategy for the synthesis and screening of dendronized polymeric carriers of different nature.
Polymers
Despite the fact that amphiphilic block copolymers have been studied in detail by various methods... more Despite the fact that amphiphilic block copolymers have been studied in detail by various methods both in common solvents and aqueous dispersions, their hydrodynamic description is still incomplete. In this paper, we present a detailed hydrodynamic study of six commercial diblock copolymers featuring the same hydrophilic block (poly(ethylene glycol), PEG; degree of polymerization is ca. 110 ± 25) and the following hydrophobic blocks: polystyrene, PS35-b-PEG115; poly(methyl methacrylate), PMMA55-b-PEG95; poly(1,4-butadyene), PBd90-b-PEG130; polyethylene PE40-b-PEG85; poly(dimethylsiloxane), PDMS15-b-PEG115; and poly(ɛ-caprolactone), PCL45-b-PEG115. The hydrodynamic properties of block copolymers are investigated in both an organic solvent (tetrahydrofuran) and in water micellar dispersions by the combination of static/dynamic light scattering, viscometry, and analytical ultracentrifugation. All the micellar dispersions demonstrate bimodal particle distributions: small compact (hydrod...
Biosensors
In the present work, we described the preparation and characterization of the micelles based on a... more In the present work, we described the preparation and characterization of the micelles based on amphiphilic poly(ε-caprolactone-block-ethylene glycol) block copolymer (PCL-b-PEG) loaded with non-symmetric [Pt(C^N*N’^C’)] complex (Pt1) (where C^N*N’^C’: 6-(phenyl(6-(thiophene-2-yl)pyridin-2-yl)amino)-2-(tyophene-2-yl)nicotinate). The obtained nanospecies displayed the ignition of near-infrared (NIR) phosphorescence upon an increase in the content of the platinum complexes in the micelles, which acted as the major emission component at 12 wt.% of Pt1. Emergence of the NIR band at 780 nm was also accompanied by a 3-fold growth of the quantum yield and an increase in the two-photon absorption cross-section that reached the value of 450 GM. Both effects are believed to be the result of progressive platinum complex aggregation inside hydrophobic poly(caprolactone) cores of block copolymer micelles, which has been ascribed to aggregation induced emission (AIE). The resulting phosphorescent...
Chemical Communications, 2022
Covalent conjugation of human serum albumin with pH-sensitive fluorescein and an Ir(iii) phosphor... more Covalent conjugation of human serum albumin with pH-sensitive fluorescein and an Ir(iii) phosphorescent complex affords a biocompatible lifetime-based dual sensor.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
The topic is the chemistry of coinage metals, and this is, in fact, a very old story (Fig. 10.1).... more The topic is the chemistry of coinage metals, and this is, in fact, a very old story (Fig. 10.1). The chemistry of coinage metals started thousand years ago with the production of pure metals, and the metals copper, silver and gold were used to cast coins.
Journal of peptide science : an official publication of the European Peptide Society, 2017
Oxime ligation is a powerful tool in various bioconjugation strategies. Nevertheless, high reacti... more Oxime ligation is a powerful tool in various bioconjugation strategies. Nevertheless, high reaction rates and quantitative yields are typically reported for aldehyde-derived compounds. In contrary, keto groups react much slower, with quantitative yields achieved at 5 h for low-molecular weight compounds and more than 15 h for polymers or dendrimers. In this communication, we report that oxime ligation proceeds rapidly with quantitative (>95%) conversion within 1.5-2 h in pure acetic acid. The practical utility of suggested technique is illustrated by the synthesis of peptide-steroid and peptide-polymer conjugates of model aminooxy-peptides. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Bioconjugate Chemistry, 2016
Molecular Pharmaceutics, 2016
Journal of Photochemistry and Photobiology A: Chemistry, 2017
Abstract The development of organelle-specific phosphorescent multiphoton probes is a rapidly gro... more Abstract The development of organelle-specific phosphorescent multiphoton probes is a rapidly growing area in biomedical imaging. Phosphorescent properties allow spectral or time-resolved discrimination from autofluorescence, while the use of two-photon microscopy provides higher spatial resolution as well as deeper penetration into the sample compared to conventional microscopies. The main challenge in this area is the design of probes that combine a complex of desired properties. Here we present investigation of the phosphorescent homoleptic alkynyl gold(I) cluster, (AuC 2 R) 10 (R − 2,6-dimethyl-4-heptanol), which combines nonlinear optical properties with selectivity to lipid droplets of adipocytes and other cells. This label reveals high two-photon absorption and emission cross-sections in hexane, good solubility in triglycerides (vegetable oil) and microsecond lifetimes both in solution and in biological tissues. These features make it a promising probe for multiphoton bioimaging as demonstrated by successful visualization of various adipose tissues (subcutaneous fat, visceral adipose tissue, adipose tissue of mesentery) of different animals (pigeon, chicken, mouse) as well as lipid droplets in Hep G2 cells. The complex demonstrates high selectivity to lipid droplets in animal tissues and cells. The probe lifetimes in microsecond domain made possible its visualization using phosphorescent lifetime imaging (PLIM) techniques.
Contrast Media & Molecular Imaging, 2015
Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis ... more Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T 1 relaxivity (6.5 mM À1 s À1 at 7 T) than the commercial agent Magnevist® (3.4 mM À1 s À1). Cellular uptake of Cx43-specific T 1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI.
Bioorganiceskaâ himiâ
A set of GnRH analogues containing nuclear localization signal (NLS) of SV-40 virus large T-antig... more A set of GnRH analogues containing nuclear localization signal (NLS) of SV-40 virus large T-antigen have been synthesized using solid phase peptide synthesis and chemical ligation technique. Selective chemical ligation was achieved as a result of hydrazone formation in the course of interaction between NLS hydrazide and GnRH analog modified by pyruvic acid. The efficiency of synthesized peptide carriers was demonstrated in experiments with human cancer cells transfected by reporter luciferase and beta-galactosidase genes or suicide HSV-1 thymidine kinase gene. It was shown that selectivity of action on cancer cells can be achieved as a result of peptide/DNA complex penetration through the cell membrane by GnRH receptor-mediated endocytosis pathway.
Using the methods of potentiometry, UV spectroscopy, and static and dynamic light scattering, the... more Using the methods of potentiometry, UV spectroscopy, and static and dynamic light scattering, the interaction of micelles of a cationic amphiphilic diblock copolymer with an oppositely charged linear homopolyelectrolyte in dilute aqueous solutions is studied. The copolymer is represented by polystyrene-block-poly(N-ethyl-4-vinylpyridinium bromide); the polyelectrolyte, by poly(methacrylic acid), and its sodium salt, sodium poly(methacrylate). As is shown, polystyrene-block-poly(N-ethyl-4-vinylpyridinium bromide) in water forms spherical micelles with the core composed of insoluble polystyrene units and the corona composed of cationic blocks of poly(N-ethyl-4-vinylpyridinium bromide); the average aggregation number is about 40. The addition of poly(methacrylic acid) or sodium polymethacrylate is accompanied by cooperative electrostatic binding of oppositely charged units, which leads to the formation of interpolyelectrolyte complexes. Depending on the charge ratio in the solution, ei...