The Experts below are selected from a list of 288 Experts worldwide ranked by ideXlab platform
Juha T. Huiskonen - One of the best experts on this subject based on the ideXlab platform.
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Double-stranded RNA virus Outer Shell assembly by bona fide domain-swapping
Nature Communications, 2017Co-Authors: Zhaoyang Sun, Kamel El Omari, Xiaoyu Sun, Serban L. Ilca, Abhay Kotecha, David I. Stuart, Minna M. Poranen, Juha T. HuiskonenAbstract:Double-Shelled bacteriophage φ6 is a well-studied model system used to understand assembly of dsRNA viruses. Here the authors report a near-atomic resolution cryo-EM structure of φ6 and propose a model for the structural transitions occurring in the Outer Shell during genome packaging. Correct Outer protein Shell assembly is a prerequisite for virion infectivity in many multi-Shelled dsRNA viruses. In the prototypic dsRNA bacteriophage φ6, the assembly reaction is promoted by calcium ions but its biomechanics remain poorly understood. Here, we describe the near-atomic resolution structure of the φ6 double-Shelled particle. The Outer T =13 Shell protein P8 consists of two alpha-helical domains joined by a linker, which allows the trimer to adopt either a closed or an open conformation. The trimers in an open conformation swap domains with each other. Our observations allow us to propose a mechanistic model for calcium concentration regulated Outer Shell assembly. Furthermore, the structure provides a prime exemplar of bona fide domain-swapping. This leads us to extend the theory of domain-swapping from the level of monomeric subunits and multimers to closed spherical Shells, and to hypothesize a mechanism by which closed protein Shells may arise in evolution.
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Double-stranded RNA virus Outer Shell assembly by bona fide domain-swapping.
Nature communications, 2017Co-Authors: Zhaoyang Sun, Xiaoyu Sun, Serban L. Ilca, Abhay Kotecha, David I. Stuart, Minna M. Poranen, Kamel El Omari, Juha T. HuiskonenAbstract:Correct Outer protein Shell assembly is a prerequisite for virion infectivity in many multi-Shelled dsRNA viruses. In the prototypic dsRNA bacteriophage φ6, the assembly reaction is promoted by calcium ions but its biomechanics remain poorly understood. Here, we describe the near-atomic resolution structure of the φ6 double-Shelled particle. The Outer T=13 Shell protein P8 consists of two alpha-helical domains joined by a linker, which allows the trimer to adopt either a closed or an open conformation. The trimers in an open conformation swap domains with each other. Our observations allow us to propose a mechanistic model for calcium concentration regulated Outer Shell assembly. Furthermore, the structure provides a prime exemplar of bona fide domain-swapping. This leads us to extend the theory of domain-swapping from the level of monomeric subunits and multimers to closed spherical Shells, and to hypothesize a mechanism by which closed protein Shells may arise in evolution.
Masao Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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effect of magnesium stearate or calcium stearate as additives on dissolution profiles of diltiazem hydrochloride from press coated tablets with hydroxypropylmethylcellulose acetate succinate in the Outer Shell
International Journal of Pharmaceutics, 2001Co-Authors: Eiji Fukui, Nobuteru Miyamura, Masao KobayashiAbstract:Effect of magnesium stearate (MgSt) or calcium stearate (CaSt) on the dissolution profiles of diltiazem hydrochloride in the core of press-coated (PC) tablets with an Outer Shell composed of hydroxypropylmethylcellulose acetate succinate (HPMCAS) was evaluated by porosity and changes in IR spectra of tablets. In JP first fluid (pH 1.2), the lag time increased with decreasing porosity and was greatest by the addition of MgSt to HPMCAS. While, in JP second fluid (pH 6.8), it increased with decreasing porosity by the addition of CaSt, but hardly changed by the addition of MgSt. Thus, using tablets prepared with the same composition as the Outer Shell, the changes in IR spectra and uptake amount of the dissolution media after immersion in first fluid and second fluid were determined. The results suggested that some physicochemical interaction occur between MgSt and HPMCAS in tablets with HPMCAS and MgSt and the uptake increased markedly in each dissolution medium. These phenomena seem to cause a prolongation of lag time in first fluid but a shortening of it in second fluid in PC tablets with HPMCAS and MgSt. In contrast, CaSt and HPMCAS did not show such interactions and increased the hydrophobic properties of the Outer Shell. Consequently, the lag time was only slightly prolonged in first fluid, however, markedly prolonged in second fluid due to suppression of second fluid penetration into micro pores in the Outer Shell and HPMCAS gel formation on the surface in PC tablets with HPMCAS and CaSt.
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An in vitro investigation of the suitability of press-coated tablets with hydroxypropylmethylcellulose acetate succinate (HPMCAS) and hydrophobic additives in the Outer Shell for colon targeting
Journal of Controlled Release, 2001Co-Authors: Eiji Fukui, Nobuteru Miyamura, Masao KobayashiAbstract:Abstract To develop a new colon targeting formulation, which can suppress drug release completely during 12 h in the stomach and release the drug rapidly after a lag time of 3±1 h in the small intestine, the use of press-coated tablets with hydroxypropylmethylcellulose acetate succinate (HPMCAS) in the Outer Shell was investigated. The release of diltiazem hydrochloride (DIL) as a model drug contained in the core tablets in the 1st fluid (pH 1.2) was suppressed by preparing with higher compression force, but the lag time in the 2nd fluid (pH 6.8) could not exceed 1.5 h. Therefore, to improve the dissolution characteristics, the effects of addition of various hydrophobic additives to HPMCAS were examined. All of the additives examined suppressed the release rate in the 1st fluid, and prolonged the lag time in the 2nd fluid compared to HPMCAS alone. However, although none of the additives examined fulfilled all of the desired criteria, magnesium stearate (MgSt) and calcium stearate (CaSt) showed interesting effects; the former suppressed drug release completely in 1st fluid, while the latter markedly prolonged the lag time in 2nd fluid. To integrate the merits of each additive, press-coated tablets with a powder mixture of HPMCAS, MgSt and CaSt in the Outer Shell (HMC tablets) were prepared and in vitro tests were performed. The results indicated that HMC tablets with a mixing ratio of 80% HPMCAS, 5–15% MgSt and 15–5% CaSt in the Outer Shell met the desired criteria and the lag time in 2nd fluid could also be controlled from 2 to 9 h. At a mixing ratio of 80% HPMCAS, 10% MgSt and 10% CaSt, the dissolution profiles of DIL in 1st fluid and 2nd fluid were not remarkably affected by agitation intensity, and addition of bile salts, pretreatment time or anticipated higher pH except for pH 6.0, respectively. These results indicated the usefulness of HMC tablets with the desirable functions for colon-targeting formulations.
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studies on applicability of press coated tablets using hydroxypropylcellulose hpc in the Outer Shell for timed release preparations
Journal of Controlled Release, 2000Co-Authors: Eiji Fukui, Katsuji Uemura, Masao KobayashiAbstract:Press-coated tablets, containing diltiazem hydrochloride (DIL) in the core tablet and coated with hydroxypropylcellulose (HPC) as the Outer Shell, were examined for applicability as timed-release tablets with a predetermined lag time and subsequent rapid drug release phase. Various types of press-coated tablets were prepared using a rotary tabletting machine and their DIL dissolution behavior was evaluated by the JP paddle method. The results indicated that tablets with the timed-release function could be prepared, and that the lag times were prolonged as the viscosity of HPC and the amount of the Outer Shell were increased. The lag times could be controlled widely by the above method, however, the compression load had little effect. Two different kinds of timed-release press-coated tablets that showed lag times of 3 and 6 h in the in vitro test (denoted PCTL3 and PCTL6, respectively) were administered to beagle dogs. DIL was first detected in the plasma more than 3 h after administration, and both tablets showed timed-release. The lag times showed a good agreement between the in vivo and in vitro tests in PCTL3. However, the in vivo lag times were about 4 h in PCTL6 and were much shorter than the in vitro lag time. The dissolution test was performed at different paddle rotation speeds, and good agreement was obtained between the in vivo and in vitro lag times at 150 rpm. This suggested that the effects of gastrointestinal peristalsis and contraction should also be taken into consideration for the further development of drug delivery systems.
Zhaoyang Sun - One of the best experts on this subject based on the ideXlab platform.
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Double-stranded RNA virus Outer Shell assembly by bona fide domain-swapping
Nature Communications, 2017Co-Authors: Zhaoyang Sun, Kamel El Omari, Xiaoyu Sun, Serban L. Ilca, Abhay Kotecha, David I. Stuart, Minna M. Poranen, Juha T. HuiskonenAbstract:Double-Shelled bacteriophage φ6 is a well-studied model system used to understand assembly of dsRNA viruses. Here the authors report a near-atomic resolution cryo-EM structure of φ6 and propose a model for the structural transitions occurring in the Outer Shell during genome packaging. Correct Outer protein Shell assembly is a prerequisite for virion infectivity in many multi-Shelled dsRNA viruses. In the prototypic dsRNA bacteriophage φ6, the assembly reaction is promoted by calcium ions but its biomechanics remain poorly understood. Here, we describe the near-atomic resolution structure of the φ6 double-Shelled particle. The Outer T =13 Shell protein P8 consists of two alpha-helical domains joined by a linker, which allows the trimer to adopt either a closed or an open conformation. The trimers in an open conformation swap domains with each other. Our observations allow us to propose a mechanistic model for calcium concentration regulated Outer Shell assembly. Furthermore, the structure provides a prime exemplar of bona fide domain-swapping. This leads us to extend the theory of domain-swapping from the level of monomeric subunits and multimers to closed spherical Shells, and to hypothesize a mechanism by which closed protein Shells may arise in evolution.
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Double-stranded RNA virus Outer Shell assembly by bona fide domain-swapping.
Nature communications, 2017Co-Authors: Zhaoyang Sun, Xiaoyu Sun, Serban L. Ilca, Abhay Kotecha, David I. Stuart, Minna M. Poranen, Kamel El Omari, Juha T. HuiskonenAbstract:Correct Outer protein Shell assembly is a prerequisite for virion infectivity in many multi-Shelled dsRNA viruses. In the prototypic dsRNA bacteriophage φ6, the assembly reaction is promoted by calcium ions but its biomechanics remain poorly understood. Here, we describe the near-atomic resolution structure of the φ6 double-Shelled particle. The Outer T=13 Shell protein P8 consists of two alpha-helical domains joined by a linker, which allows the trimer to adopt either a closed or an open conformation. The trimers in an open conformation swap domains with each other. Our observations allow us to propose a mechanistic model for calcium concentration regulated Outer Shell assembly. Furthermore, the structure provides a prime exemplar of bona fide domain-swapping. This leads us to extend the theory of domain-swapping from the level of monomeric subunits and multimers to closed spherical Shells, and to hypothesize a mechanism by which closed protein Shells may arise in evolution.
Eiji Fukui - One of the best experts on this subject based on the ideXlab platform.
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effect of magnesium stearate or calcium stearate as additives on dissolution profiles of diltiazem hydrochloride from press coated tablets with hydroxypropylmethylcellulose acetate succinate in the Outer Shell
International Journal of Pharmaceutics, 2001Co-Authors: Eiji Fukui, Nobuteru Miyamura, Masao KobayashiAbstract:Effect of magnesium stearate (MgSt) or calcium stearate (CaSt) on the dissolution profiles of diltiazem hydrochloride in the core of press-coated (PC) tablets with an Outer Shell composed of hydroxypropylmethylcellulose acetate succinate (HPMCAS) was evaluated by porosity and changes in IR spectra of tablets. In JP first fluid (pH 1.2), the lag time increased with decreasing porosity and was greatest by the addition of MgSt to HPMCAS. While, in JP second fluid (pH 6.8), it increased with decreasing porosity by the addition of CaSt, but hardly changed by the addition of MgSt. Thus, using tablets prepared with the same composition as the Outer Shell, the changes in IR spectra and uptake amount of the dissolution media after immersion in first fluid and second fluid were determined. The results suggested that some physicochemical interaction occur between MgSt and HPMCAS in tablets with HPMCAS and MgSt and the uptake increased markedly in each dissolution medium. These phenomena seem to cause a prolongation of lag time in first fluid but a shortening of it in second fluid in PC tablets with HPMCAS and MgSt. In contrast, CaSt and HPMCAS did not show such interactions and increased the hydrophobic properties of the Outer Shell. Consequently, the lag time was only slightly prolonged in first fluid, however, markedly prolonged in second fluid due to suppression of second fluid penetration into micro pores in the Outer Shell and HPMCAS gel formation on the surface in PC tablets with HPMCAS and CaSt.
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An in vitro investigation of the suitability of press-coated tablets with hydroxypropylmethylcellulose acetate succinate (HPMCAS) and hydrophobic additives in the Outer Shell for colon targeting
Journal of Controlled Release, 2001Co-Authors: Eiji Fukui, Nobuteru Miyamura, Masao KobayashiAbstract:Abstract To develop a new colon targeting formulation, which can suppress drug release completely during 12 h in the stomach and release the drug rapidly after a lag time of 3±1 h in the small intestine, the use of press-coated tablets with hydroxypropylmethylcellulose acetate succinate (HPMCAS) in the Outer Shell was investigated. The release of diltiazem hydrochloride (DIL) as a model drug contained in the core tablets in the 1st fluid (pH 1.2) was suppressed by preparing with higher compression force, but the lag time in the 2nd fluid (pH 6.8) could not exceed 1.5 h. Therefore, to improve the dissolution characteristics, the effects of addition of various hydrophobic additives to HPMCAS were examined. All of the additives examined suppressed the release rate in the 1st fluid, and prolonged the lag time in the 2nd fluid compared to HPMCAS alone. However, although none of the additives examined fulfilled all of the desired criteria, magnesium stearate (MgSt) and calcium stearate (CaSt) showed interesting effects; the former suppressed drug release completely in 1st fluid, while the latter markedly prolonged the lag time in 2nd fluid. To integrate the merits of each additive, press-coated tablets with a powder mixture of HPMCAS, MgSt and CaSt in the Outer Shell (HMC tablets) were prepared and in vitro tests were performed. The results indicated that HMC tablets with a mixing ratio of 80% HPMCAS, 5–15% MgSt and 15–5% CaSt in the Outer Shell met the desired criteria and the lag time in 2nd fluid could also be controlled from 2 to 9 h. At a mixing ratio of 80% HPMCAS, 10% MgSt and 10% CaSt, the dissolution profiles of DIL in 1st fluid and 2nd fluid were not remarkably affected by agitation intensity, and addition of bile salts, pretreatment time or anticipated higher pH except for pH 6.0, respectively. These results indicated the usefulness of HMC tablets with the desirable functions for colon-targeting formulations.
-
studies on applicability of press coated tablets using hydroxypropylcellulose hpc in the Outer Shell for timed release preparations
Journal of Controlled Release, 2000Co-Authors: Eiji Fukui, Katsuji Uemura, Masao KobayashiAbstract:Press-coated tablets, containing diltiazem hydrochloride (DIL) in the core tablet and coated with hydroxypropylcellulose (HPC) as the Outer Shell, were examined for applicability as timed-release tablets with a predetermined lag time and subsequent rapid drug release phase. Various types of press-coated tablets were prepared using a rotary tabletting machine and their DIL dissolution behavior was evaluated by the JP paddle method. The results indicated that tablets with the timed-release function could be prepared, and that the lag times were prolonged as the viscosity of HPC and the amount of the Outer Shell were increased. The lag times could be controlled widely by the above method, however, the compression load had little effect. Two different kinds of timed-release press-coated tablets that showed lag times of 3 and 6 h in the in vitro test (denoted PCTL3 and PCTL6, respectively) were administered to beagle dogs. DIL was first detected in the plasma more than 3 h after administration, and both tablets showed timed-release. The lag times showed a good agreement between the in vivo and in vitro tests in PCTL3. However, the in vivo lag times were about 4 h in PCTL6 and were much shorter than the in vitro lag time. The dissolution test was performed at different paddle rotation speeds, and good agreement was obtained between the in vivo and in vitro lag times at 150 rpm. This suggested that the effects of gastrointestinal peristalsis and contraction should also be taken into consideration for the further development of drug delivery systems.
Minna M. Poranen - One of the best experts on this subject based on the ideXlab platform.
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Double-stranded RNA virus Outer Shell assembly by bona fide domain-swapping
Nature Communications, 2017Co-Authors: Zhaoyang Sun, Kamel El Omari, Xiaoyu Sun, Serban L. Ilca, Abhay Kotecha, David I. Stuart, Minna M. Poranen, Juha T. HuiskonenAbstract:Double-Shelled bacteriophage φ6 is a well-studied model system used to understand assembly of dsRNA viruses. Here the authors report a near-atomic resolution cryo-EM structure of φ6 and propose a model for the structural transitions occurring in the Outer Shell during genome packaging. Correct Outer protein Shell assembly is a prerequisite for virion infectivity in many multi-Shelled dsRNA viruses. In the prototypic dsRNA bacteriophage φ6, the assembly reaction is promoted by calcium ions but its biomechanics remain poorly understood. Here, we describe the near-atomic resolution structure of the φ6 double-Shelled particle. The Outer T =13 Shell protein P8 consists of two alpha-helical domains joined by a linker, which allows the trimer to adopt either a closed or an open conformation. The trimers in an open conformation swap domains with each other. Our observations allow us to propose a mechanistic model for calcium concentration regulated Outer Shell assembly. Furthermore, the structure provides a prime exemplar of bona fide domain-swapping. This leads us to extend the theory of domain-swapping from the level of monomeric subunits and multimers to closed spherical Shells, and to hypothesize a mechanism by which closed protein Shells may arise in evolution.
-
Double-stranded RNA virus Outer Shell assembly by bona fide domain-swapping.
Nature communications, 2017Co-Authors: Zhaoyang Sun, Xiaoyu Sun, Serban L. Ilca, Abhay Kotecha, David I. Stuart, Minna M. Poranen, Kamel El Omari, Juha T. HuiskonenAbstract:Correct Outer protein Shell assembly is a prerequisite for virion infectivity in many multi-Shelled dsRNA viruses. In the prototypic dsRNA bacteriophage φ6, the assembly reaction is promoted by calcium ions but its biomechanics remain poorly understood. Here, we describe the near-atomic resolution structure of the φ6 double-Shelled particle. The Outer T=13 Shell protein P8 consists of two alpha-helical domains joined by a linker, which allows the trimer to adopt either a closed or an open conformation. The trimers in an open conformation swap domains with each other. Our observations allow us to propose a mechanistic model for calcium concentration regulated Outer Shell assembly. Furthermore, the structure provides a prime exemplar of bona fide domain-swapping. This leads us to extend the theory of domain-swapping from the level of monomeric subunits and multimers to closed spherical Shells, and to hypothesize a mechanism by which closed protein Shells may arise in evolution.
