Siamak Shoravi | Linnaeus University (original) (raw)
Papers by Siamak Shoravi
International journal of molecular sciences, 2014
Aspects of the molecular-level basis for the function of ethylene glycol dimethacrylate and trime... more Aspects of the molecular-level basis for the function of ethylene glycol dimethacrylate and trimethylolproprane trimethacrylate crosslinked methacrylic acid copolymers molecularly imprinted with (S)-propranolol have been studied using a series of all-component and all-atom molecular dynamics studies of the corresponding prepolymerization systems. The crosslinking agents were observed to contribute to template complexation, and the results were contrasted with previously reported template-recognition behavior of the corresponding polymers. Differences in the extent to which the two crosslinkers interacted with the functional monomer were identified, and correlations were made to polymer-ligand recognition behavior and the results of nuclear magnetic resonance spectroscopic studies studies. This study demonstrates the importance of considering the functional monomer-crosslinker interaction when designing molecularly imprinted polymers, and highlights the often neglected general contri...
Principles and Applications of Micro- and Nanostructure Polymers, 2013
Journal of Molecular Recognition, 2012
A series of molecular dynamics simulations of prepolymerization mixtures for phenylalanine anilid... more A series of molecular dynamics simulations of prepolymerization mixtures for phenylalanine anilide imprinted co-(ethylene glycol dimethacrylate-methacrylic acid) molecularly imprinted polymers have been employed to investigate the mechanistic basis for template selective recognition in these systems. This has provided new insights on the mechanisms underlying template recognition, in particular the significant role played by the crosslinking agent. Importantly, the study supports the occurrence of template self-association events that allows us to resolve debate between the two previously proposed models used to explain this system's underlying recognition mechanisms. Moreover, the complexity of the molecular level events underlying template complexation is highlighted by this study, a factor that should be considered in rational molecularly imprinted polymer design, especially with respect to recognition site heterogeneity.
Org. Biomol. Chem., 2016
All-component molecular dynamics studies were used to probe a library of oseltamivir molecularly ... more All-component molecular dynamics studies were used to probe a library of oseltamivir molecularly imprinted polymer prepolymerization mixtures. Polymers included one of five functional monomers (acrylamide, hydroxyethylmethacrylate, methacrylic acid, 2-(triflouromethyl)acrylic acid, 4-vinylpyridine) and one of three porogens (acetonitrile, chloroform, methanol) combined with the crosslinking agent ethylene glycol dimethacrylate and initiator 2,2'-azobis(2-methylpropionitrile). Polymers were characterized by nitrogen gas sorption measurements and SEM, and affinity studies performed using radioligand binding in various media. In agreement with the predictions made from the simulations, polymers prepared in acetonitrile using either methacrylic or trifluoromethacrylic acid demonstrated the highest affinities for oseltamivir. Further, the ensemble of interactions observed in the methanol system provided an explanation for the morphology of polymers prepared in this solvent. The materials developed here offer potential for use in solid-phase extraction or for catalysis. The results illustrate the strength of this in silico strategy as a potential prognostic tool in molecularly imprinted polymer design.
Tetrahedron Asymmetry, Aug 1, 2004
Polymeric chiral reductants selective for the reduction of ())-menthone 1 to the diastereomeric p... more Polymeric chiral reductants selective for the reduction of ())-menthone 1 to the diastereomeric products ())-menthol 2 and (+)-neomenthol 3 were prepared by a covalent molecular imprinting using 2 as the template. The LiAlH 4 derivatized imprinted polymers altered the natural outcome of the reduction reaction (LiAlH 4 ) from 2:1 [())-menthol:(+)-neomenthol] to 1:1. The reaction mechanism is discussed in terms of reaction site structure. The molecularly imprinted polymers demonstrated enantioselective recognition for 2 (0.15 lmol enantioselective sites/g polymer) in batch binding experiments.
ABSTRACT The present invention relates to a method of screening a biol. target for transient weak... more ABSTRACT The present invention relates to a method of screening a biol. target for transient weak interactions between the target and a library of ligands. The method includes the provision of a compn. comprising a biol. target and the provision of a plurality of stationary phases from such a compn. A plurality of ligand compns. is transported to the stationary phases to establish contacts between the ligands and the biol. targets. Zonal retardation information are collected for each ligand, downstream of the stationary phases in order to select ligands with dissocn. consts. (Kd) in the range of 0.01 to 10 mM, exhibiting weak affinity to the target. [on SciFinder(R)]
The present invention relates to a method of screening a biol. target for transient weak interact... more The present invention relates to a method of screening a biol. target for transient weak interactions between the target and a library of ligands. The method includes the provision of a compn. comprising a biol. target and the provision of a plurality of stationary phases from such a compn. A plurality of ligand compns. is transported to the stationary phases to establish contacts between the ligands and the biol. targets. Zonal retardation information are collected for each ligand, downstream of the stationary phases in order to select ligands with dissocn. consts. (Kd) in the range of 0.01 to 10 mM, exhibiting weak affinity to the target. [on SciFinder(R)]
International journal of molecular sciences, 2014
Aspects of the molecular-level basis for the function of ethylene glycol dimethacrylate and trime... more Aspects of the molecular-level basis for the function of ethylene glycol dimethacrylate and trimethylolproprane trimethacrylate crosslinked methacrylic acid copolymers molecularly imprinted with (S)-propranolol have been studied using a series of all-component and all-atom molecular dynamics studies of the corresponding prepolymerization systems. The crosslinking agents were observed to contribute to template complexation, and the results were contrasted with previously reported template-recognition behavior of the corresponding polymers. Differences in the extent to which the two crosslinkers interacted with the functional monomer were identified, and correlations were made to polymer-ligand recognition behavior and the results of nuclear magnetic resonance spectroscopic studies studies. This study demonstrates the importance of considering the functional monomer-crosslinker interaction when designing molecularly imprinted polymers, and highlights the often neglected general contri...
Principles and Applications of Micro- and Nanostructure Polymers, 2013
Tetrahedron: Asymmetry, 2004
Polymeric chiral reductants selective for the reduction of ())-menthone 1 to the diastereomeric p... more Polymeric chiral reductants selective for the reduction of ())-menthone 1 to the diastereomeric products ())-menthol 2 and (+)-neomenthol 3 were prepared by a covalent molecular imprinting using 2 as the template. The LiAlH 4 derivatized imprinted polymers altered the natural outcome of the reduction reaction (LiAlH 4 ) from 2:1 [())-menthol:(+)-neomenthol] to 1:1. The reaction mechanism is discussed in terms of reaction site structure. The molecularly imprinted polymers demonstrated enantioselective recognition for 2 (0.15 lmol enantioselective sites/g polymer) in batch binding experiments.
Journal of Molecular Recognition, 2012
A series of molecular dynamics simulations of prepolymerization mixtures for phenylalanine anilid... more A series of molecular dynamics simulations of prepolymerization mixtures for phenylalanine anilide imprinted co-(ethylene glycol dimethacrylate-methacrylic acid) molecularly imprinted polymers have been employed to investigate the mechanistic basis for template selective recognition in these systems. This has provided new insights on the mechanisms underlying template recognition, in particular the significant role played by the crosslinking agent. Importantly, the study supports the occurrence of template self-association events that allows us to resolve debate between the two previously proposed models used to explain this system's underlying recognition mechanisms. Moreover, the complexity of the molecular level events underlying template complexation is highlighted by this study, a factor that should be considered in rational molecularly imprinted polymer design, especially with respect to recognition site heterogeneity.
Analytical Biochemistry, 2006
The notion that many biological interactions are based on transient binding (dissociation constan... more The notion that many biological interactions are based on transient binding (dissociation constants (K d ) in the range of 10-0.01 mM) is familiar, yet the implications for biological sciences have been realized only recently. An important area of biological sciences is drug design, where the traditional "lock and key" view of binding has prevailed and drug candidates are usually selected on their merits as being tight binders. However, the rationale that transient interactions are of importance for drug discovery is slowly gaining acceptance. These interactions may relate not only to the desired target interaction but also to unwanted interactions creating, for example, toxicity problems. Here we demonstrate, in a high-throughput screening format, aYnity selection of weak binders to a model target of albumin by zonal retardation chromatography. It is perceived that this approach can deWne the "transient drug" as a complement to current drug discovery procedures.
International journal of molecular sciences, 2014
Aspects of the molecular-level basis for the function of ethylene glycol dimethacrylate and trime... more Aspects of the molecular-level basis for the function of ethylene glycol dimethacrylate and trimethylolproprane trimethacrylate crosslinked methacrylic acid copolymers molecularly imprinted with (S)-propranolol have been studied using a series of all-component and all-atom molecular dynamics studies of the corresponding prepolymerization systems. The crosslinking agents were observed to contribute to template complexation, and the results were contrasted with previously reported template-recognition behavior of the corresponding polymers. Differences in the extent to which the two crosslinkers interacted with the functional monomer were identified, and correlations were made to polymer-ligand recognition behavior and the results of nuclear magnetic resonance spectroscopic studies studies. This study demonstrates the importance of considering the functional monomer-crosslinker interaction when designing molecularly imprinted polymers, and highlights the often neglected general contri...
Principles and Applications of Micro- and Nanostructure Polymers, 2013
Journal of Molecular Recognition, 2012
A series of molecular dynamics simulations of prepolymerization mixtures for phenylalanine anilid... more A series of molecular dynamics simulations of prepolymerization mixtures for phenylalanine anilide imprinted co-(ethylene glycol dimethacrylate-methacrylic acid) molecularly imprinted polymers have been employed to investigate the mechanistic basis for template selective recognition in these systems. This has provided new insights on the mechanisms underlying template recognition, in particular the significant role played by the crosslinking agent. Importantly, the study supports the occurrence of template self-association events that allows us to resolve debate between the two previously proposed models used to explain this system's underlying recognition mechanisms. Moreover, the complexity of the molecular level events underlying template complexation is highlighted by this study, a factor that should be considered in rational molecularly imprinted polymer design, especially with respect to recognition site heterogeneity.
Org. Biomol. Chem., 2016
All-component molecular dynamics studies were used to probe a library of oseltamivir molecularly ... more All-component molecular dynamics studies were used to probe a library of oseltamivir molecularly imprinted polymer prepolymerization mixtures. Polymers included one of five functional monomers (acrylamide, hydroxyethylmethacrylate, methacrylic acid, 2-(triflouromethyl)acrylic acid, 4-vinylpyridine) and one of three porogens (acetonitrile, chloroform, methanol) combined with the crosslinking agent ethylene glycol dimethacrylate and initiator 2,2'-azobis(2-methylpropionitrile). Polymers were characterized by nitrogen gas sorption measurements and SEM, and affinity studies performed using radioligand binding in various media. In agreement with the predictions made from the simulations, polymers prepared in acetonitrile using either methacrylic or trifluoromethacrylic acid demonstrated the highest affinities for oseltamivir. Further, the ensemble of interactions observed in the methanol system provided an explanation for the morphology of polymers prepared in this solvent. The materials developed here offer potential for use in solid-phase extraction or for catalysis. The results illustrate the strength of this in silico strategy as a potential prognostic tool in molecularly imprinted polymer design.
Tetrahedron Asymmetry, Aug 1, 2004
Polymeric chiral reductants selective for the reduction of ())-menthone 1 to the diastereomeric p... more Polymeric chiral reductants selective for the reduction of ())-menthone 1 to the diastereomeric products ())-menthol 2 and (+)-neomenthol 3 were prepared by a covalent molecular imprinting using 2 as the template. The LiAlH 4 derivatized imprinted polymers altered the natural outcome of the reduction reaction (LiAlH 4 ) from 2:1 [())-menthol:(+)-neomenthol] to 1:1. The reaction mechanism is discussed in terms of reaction site structure. The molecularly imprinted polymers demonstrated enantioselective recognition for 2 (0.15 lmol enantioselective sites/g polymer) in batch binding experiments.
ABSTRACT The present invention relates to a method of screening a biol. target for transient weak... more ABSTRACT The present invention relates to a method of screening a biol. target for transient weak interactions between the target and a library of ligands. The method includes the provision of a compn. comprising a biol. target and the provision of a plurality of stationary phases from such a compn. A plurality of ligand compns. is transported to the stationary phases to establish contacts between the ligands and the biol. targets. Zonal retardation information are collected for each ligand, downstream of the stationary phases in order to select ligands with dissocn. consts. (Kd) in the range of 0.01 to 10 mM, exhibiting weak affinity to the target. [on SciFinder(R)]
The present invention relates to a method of screening a biol. target for transient weak interact... more The present invention relates to a method of screening a biol. target for transient weak interactions between the target and a library of ligands. The method includes the provision of a compn. comprising a biol. target and the provision of a plurality of stationary phases from such a compn. A plurality of ligand compns. is transported to the stationary phases to establish contacts between the ligands and the biol. targets. Zonal retardation information are collected for each ligand, downstream of the stationary phases in order to select ligands with dissocn. consts. (Kd) in the range of 0.01 to 10 mM, exhibiting weak affinity to the target. [on SciFinder(R)]
International journal of molecular sciences, 2014
Aspects of the molecular-level basis for the function of ethylene glycol dimethacrylate and trime... more Aspects of the molecular-level basis for the function of ethylene glycol dimethacrylate and trimethylolproprane trimethacrylate crosslinked methacrylic acid copolymers molecularly imprinted with (S)-propranolol have been studied using a series of all-component and all-atom molecular dynamics studies of the corresponding prepolymerization systems. The crosslinking agents were observed to contribute to template complexation, and the results were contrasted with previously reported template-recognition behavior of the corresponding polymers. Differences in the extent to which the two crosslinkers interacted with the functional monomer were identified, and correlations were made to polymer-ligand recognition behavior and the results of nuclear magnetic resonance spectroscopic studies studies. This study demonstrates the importance of considering the functional monomer-crosslinker interaction when designing molecularly imprinted polymers, and highlights the often neglected general contri...
Principles and Applications of Micro- and Nanostructure Polymers, 2013
Tetrahedron: Asymmetry, 2004
Polymeric chiral reductants selective for the reduction of ())-menthone 1 to the diastereomeric p... more Polymeric chiral reductants selective for the reduction of ())-menthone 1 to the diastereomeric products ())-menthol 2 and (+)-neomenthol 3 were prepared by a covalent molecular imprinting using 2 as the template. The LiAlH 4 derivatized imprinted polymers altered the natural outcome of the reduction reaction (LiAlH 4 ) from 2:1 [())-menthol:(+)-neomenthol] to 1:1. The reaction mechanism is discussed in terms of reaction site structure. The molecularly imprinted polymers demonstrated enantioselective recognition for 2 (0.15 lmol enantioselective sites/g polymer) in batch binding experiments.
Journal of Molecular Recognition, 2012
A series of molecular dynamics simulations of prepolymerization mixtures for phenylalanine anilid... more A series of molecular dynamics simulations of prepolymerization mixtures for phenylalanine anilide imprinted co-(ethylene glycol dimethacrylate-methacrylic acid) molecularly imprinted polymers have been employed to investigate the mechanistic basis for template selective recognition in these systems. This has provided new insights on the mechanisms underlying template recognition, in particular the significant role played by the crosslinking agent. Importantly, the study supports the occurrence of template self-association events that allows us to resolve debate between the two previously proposed models used to explain this system's underlying recognition mechanisms. Moreover, the complexity of the molecular level events underlying template complexation is highlighted by this study, a factor that should be considered in rational molecularly imprinted polymer design, especially with respect to recognition site heterogeneity.
Analytical Biochemistry, 2006
The notion that many biological interactions are based on transient binding (dissociation constan... more The notion that many biological interactions are based on transient binding (dissociation constants (K d ) in the range of 10-0.01 mM) is familiar, yet the implications for biological sciences have been realized only recently. An important area of biological sciences is drug design, where the traditional "lock and key" view of binding has prevailed and drug candidates are usually selected on their merits as being tight binders. However, the rationale that transient interactions are of importance for drug discovery is slowly gaining acceptance. These interactions may relate not only to the desired target interaction but also to unwanted interactions creating, for example, toxicity problems. Here we demonstrate, in a high-throughput screening format, aYnity selection of weak binders to a model target of albumin by zonal retardation chromatography. It is perceived that this approach can deWne the "transient drug" as a complement to current drug discovery procedures.