The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
Vern L Schramm - One of the best experts on this subject based on the ideXlab platform.
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a β fluoroamine inhibitor of Purine Nucleoside Phosphorylase
Journal of Medicinal Chemistry, 2008Co-Authors: Jennifer M Mason, Vern L Schramm, Graeme J Gainsford, Andrew S Murkin, Brian W SkeltonAbstract:The potent immucillin Purine Nucleoside Phosphorylase (PNP) inhibitors F-DADMe-ImmH [(3S,4S)-3], and [(3R,4R)-3] are synthesized in seven steps. Cycloaddition to a fluoroalkene and an enzymic resolution are the key features of the construction of the fluoropyrrolidines 11, from which the immucillins are assembled by use of a three-component Mannich reaction. Slow-onset binding constants (Ki∗) for [(3S,4S)-3] and [(3R,4R)-3] with human PNP are 0.032 and 1.82 nM, respectively. F-DADMe-ImmH [(3S,4S)-3] exhibits oral availability in mice at doses as low as 0.2 mg/kg.
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l enantiomers of transition state analogue inhibitors bound to human Purine Nucleoside Phosphorylase
Journal of the American Chemical Society, 2008Co-Authors: Agnes Rinaldomatthis, Gary B Evans, Richard H Furneaux, Peter C Tyler, Steven C Almo, Andrew S Murkin, Udupi A Ramagopal, Keith Clinch, Simon P H Mee, Vern L SchrammAbstract:Human Purine Nucleoside Phosphorylase (PNP) was crystallized with transition-state analogue inhibitors Immucillin-H and DADMe-Immucillin-H synthesized with ribosyl mimics of l-stereochemistry. The inhibitors demonstrate that major driving forces for tight binding of these analogues are the leaving group interaction and the cationic mimicry of the transition state, even though large geometric changes occur with d-Immucillins and l-Immucillins bound to human PNP.
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Phosphate activation in the ground state of Purine Nucleoside Phosphorylase.
Journal of the American Chemical Society, 2006Co-Authors: Hua Deng, And Andrew S. Murkin, Vern L SchrammAbstract:Phosphate and ribose 1-phosphate (R1P) bound to human Purine Nucleoside Phosphorylase (PNP) have been studied by FTIR spectroscopy for comparison with phosphate bound with a transition state analog...
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synthesis of a transition state analogue inhibitor of Purine Nucleoside Phosphorylase via the mannich reaction
Organic Letters, 2003Co-Authors: Gary B Evans, Richard H Furneaux, Peter C Tyler, Vern L SchrammAbstract:The expeditious convergent synthesis of the potent human Purine Nucleoside Phosphorylase inhibitor DADMe-Immucillin-G (3) was achieved via the Mannich reaction. The Mannich chemistry of a series of deazaPurines and amine hydrochlorides was also investigated.
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Exploring Structure−Activity Relationships of Transition State Analogues of Human Purine Nucleoside Phosphorylase
Journal of medicinal chemistry, 2003Co-Authors: Gary B Evans, Richard H Furneaux, Andrzej Lewandowicz, Vern L Schramm, Peter C TylerAbstract:The aza-C-Nucleosides, Immucillin-H and Immucillin-G, are transition state analogue inhibitors of Purine Nucleoside Phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2‘-, 3‘-, or 5‘-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazaPurine, as well as methylene-bridged analogues, have been synthesized and tested for their inhibition of human Purine Nucleoside Phosphorylase. All analogues were poorer inhibitors, which reflects the superior capture of transition state features in the parent immucillins.
Peter C Tyler - One of the best experts on this subject based on the ideXlab platform.
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l enantiomers of transition state analogue inhibitors bound to human Purine Nucleoside Phosphorylase
Journal of the American Chemical Society, 2008Co-Authors: Agnes Rinaldomatthis, Gary B Evans, Richard H Furneaux, Peter C Tyler, Steven C Almo, Andrew S Murkin, Udupi A Ramagopal, Keith Clinch, Simon P H Mee, Vern L SchrammAbstract:Human Purine Nucleoside Phosphorylase (PNP) was crystallized with transition-state analogue inhibitors Immucillin-H and DADMe-Immucillin-H synthesized with ribosyl mimics of l-stereochemistry. The inhibitors demonstrate that major driving forces for tight binding of these analogues are the leaving group interaction and the cationic mimicry of the transition state, even though large geometric changes occur with d-Immucillins and l-Immucillins bound to human PNP.
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synthesis of a transition state analogue inhibitor of Purine Nucleoside Phosphorylase via the mannich reaction
Organic Letters, 2003Co-Authors: Gary B Evans, Richard H Furneaux, Peter C Tyler, Vern L SchrammAbstract:The expeditious convergent synthesis of the potent human Purine Nucleoside Phosphorylase inhibitor DADMe-Immucillin-G (3) was achieved via the Mannich reaction. The Mannich chemistry of a series of deazaPurines and amine hydrochlorides was also investigated.
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Exploring Structure−Activity Relationships of Transition State Analogues of Human Purine Nucleoside Phosphorylase
Journal of medicinal chemistry, 2003Co-Authors: Gary B Evans, Richard H Furneaux, Andrzej Lewandowicz, Vern L Schramm, Peter C TylerAbstract:The aza-C-Nucleosides, Immucillin-H and Immucillin-G, are transition state analogue inhibitors of Purine Nucleoside Phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2‘-, 3‘-, or 5‘-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazaPurine, as well as methylene-bridged analogues, have been synthesized and tested for their inhibition of human Purine Nucleoside Phosphorylase. All analogues were poorer inhibitors, which reflects the superior capture of transition state features in the parent immucillins.
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exploring structure activity relationships of transition state analogues of human Purine Nucleoside Phosphorylase
Journal of Medicinal Chemistry, 2003Co-Authors: Gary B Evans, Richard H Furneaux, Andrzej Lewandowicz, Vern L Schramm, Peter C TylerAbstract:The aza-C-Nucleosides, Immucillin-H and Immucillin-G, are transition state analogue inhibitors of Purine Nucleoside Phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2‘-, 3‘-, or 5‘-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazaPurine, as well as methylene-bridged analogues, have been synthesized and tested for their inhibition of human Purine Nucleoside Phosphorylase. All analogues were poorer inhibitors, which reflects the superior capture of transition state features in the parent immucillins.
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synthesis of transition state analogue inhibitors for Purine Nucleoside Phosphorylase and n riboside hydrolases
Tetrahedron, 2000Co-Authors: Gary B Evans, Richard H Furneaux, Vern L Schramm, Graeme J Gainsford, Peter C TylerAbstract:Abstract Syntheses of the ‘Immucillins’, potent aza-C-Nucleoside inhibitors of Purine Nucleoside Phosphorylase are reported as well as those of 5-deoxy-, 5-deoxyfluoro- and 2-deoxy- analogues and others having modified bases.
Leila Parvaneh - One of the best experts on this subject based on the ideXlab platform.
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Case report Progressive multifocal leukoencephalopathy in Purine Nucleoside Phosphorylase deficiency
2007Co-Authors: Nima Parvaneh, Nima Pouladi, Fatemeh Sayarifar, Mehdi Yeganeh, Mahmoud Reza Ashrafi, Leila ParvanehAbstract:Progressive multifocal leukoencephalopathy is a demyelinating disease caused by JC virus, an opportunistic infection of the central nervous system. Although the majority of cases are infected with the human immunodeficiency virus (HIV), other immunocompromised patients are also at risk. Purine Nucleoside Phosphorylase is an enzyme in the Purine salvage pathway that reversibly converts inosine to hypoxanthine and guanosine to guanine. Purine Nucleoside Phosphorylase deficiency is a combined immunodeficiency with a profound cellular defect. Neurologic abnormalities are salient features of this syndrome. We describe for the first time a patient with this rare disorder presented with progressive multifocal leukoencephalopathy. 2006 Elsevier B.V. All rights reserved.
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Progressive multifocal leukoencephalopathy in Purine Nucleoside Phosphorylase deficiency.
Brain & Development, 2006Co-Authors: Nima Parvaneh, Nima Pouladi, Fatemeh Sayarifar, Mehdi Yeganeh, Mahmoud Reza Ashrafi, Leila ParvanehAbstract:Progressive multifocal leukoencephalopathy is a demyelinating disease caused by JC virus, an opportunistic infection of the central nervous system. Although the majority of cases are infected with the human immunodeficiency virus (HIV), other immunocompromised patients are also at risk. Purine Nucleoside Phosphorylase is an enzyme in the Purine salvage pathway that reversibly converts inosine to hypoxanthine and guanosine to guanine. Purine Nucleoside Phosphorylase deficiency is a combined immunodeficiency with a profound cellular defect. Neurologic abnormalities are salient features of this syndrome. We describe for the first time a patient with this rare disorder presented with progressive multifocal leukoencephalopathy.
Richard H Furneaux - One of the best experts on this subject based on the ideXlab platform.
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l enantiomers of transition state analogue inhibitors bound to human Purine Nucleoside Phosphorylase
Journal of the American Chemical Society, 2008Co-Authors: Agnes Rinaldomatthis, Gary B Evans, Richard H Furneaux, Peter C Tyler, Steven C Almo, Andrew S Murkin, Udupi A Ramagopal, Keith Clinch, Simon P H Mee, Vern L SchrammAbstract:Human Purine Nucleoside Phosphorylase (PNP) was crystallized with transition-state analogue inhibitors Immucillin-H and DADMe-Immucillin-H synthesized with ribosyl mimics of l-stereochemistry. The inhibitors demonstrate that major driving forces for tight binding of these analogues are the leaving group interaction and the cationic mimicry of the transition state, even though large geometric changes occur with d-Immucillins and l-Immucillins bound to human PNP.
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synthesis of a transition state analogue inhibitor of Purine Nucleoside Phosphorylase via the mannich reaction
Organic Letters, 2003Co-Authors: Gary B Evans, Richard H Furneaux, Peter C Tyler, Vern L SchrammAbstract:The expeditious convergent synthesis of the potent human Purine Nucleoside Phosphorylase inhibitor DADMe-Immucillin-G (3) was achieved via the Mannich reaction. The Mannich chemistry of a series of deazaPurines and amine hydrochlorides was also investigated.
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Exploring Structure−Activity Relationships of Transition State Analogues of Human Purine Nucleoside Phosphorylase
Journal of medicinal chemistry, 2003Co-Authors: Gary B Evans, Richard H Furneaux, Andrzej Lewandowicz, Vern L Schramm, Peter C TylerAbstract:The aza-C-Nucleosides, Immucillin-H and Immucillin-G, are transition state analogue inhibitors of Purine Nucleoside Phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2‘-, 3‘-, or 5‘-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazaPurine, as well as methylene-bridged analogues, have been synthesized and tested for their inhibition of human Purine Nucleoside Phosphorylase. All analogues were poorer inhibitors, which reflects the superior capture of transition state features in the parent immucillins.
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exploring structure activity relationships of transition state analogues of human Purine Nucleoside Phosphorylase
Journal of Medicinal Chemistry, 2003Co-Authors: Gary B Evans, Richard H Furneaux, Andrzej Lewandowicz, Vern L Schramm, Peter C TylerAbstract:The aza-C-Nucleosides, Immucillin-H and Immucillin-G, are transition state analogue inhibitors of Purine Nucleoside Phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2‘-, 3‘-, or 5‘-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazaPurine, as well as methylene-bridged analogues, have been synthesized and tested for their inhibition of human Purine Nucleoside Phosphorylase. All analogues were poorer inhibitors, which reflects the superior capture of transition state features in the parent immucillins.
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synthesis of transition state analogue inhibitors for Purine Nucleoside Phosphorylase and n riboside hydrolases
Tetrahedron, 2000Co-Authors: Gary B Evans, Richard H Furneaux, Vern L Schramm, Graeme J Gainsford, Peter C TylerAbstract:Abstract Syntheses of the ‘Immucillins’, potent aza-C-Nucleoside inhibitors of Purine Nucleoside Phosphorylase are reported as well as those of 5-deoxy-, 5-deoxyfluoro- and 2-deoxy- analogues and others having modified bases.
Gary B Evans - One of the best experts on this subject based on the ideXlab platform.
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l enantiomers of transition state analogue inhibitors bound to human Purine Nucleoside Phosphorylase
Journal of the American Chemical Society, 2008Co-Authors: Agnes Rinaldomatthis, Gary B Evans, Richard H Furneaux, Peter C Tyler, Steven C Almo, Andrew S Murkin, Udupi A Ramagopal, Keith Clinch, Simon P H Mee, Vern L SchrammAbstract:Human Purine Nucleoside Phosphorylase (PNP) was crystallized with transition-state analogue inhibitors Immucillin-H and DADMe-Immucillin-H synthesized with ribosyl mimics of l-stereochemistry. The inhibitors demonstrate that major driving forces for tight binding of these analogues are the leaving group interaction and the cationic mimicry of the transition state, even though large geometric changes occur with d-Immucillins and l-Immucillins bound to human PNP.
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synthesis of a transition state analogue inhibitor of Purine Nucleoside Phosphorylase via the mannich reaction
Organic Letters, 2003Co-Authors: Gary B Evans, Richard H Furneaux, Peter C Tyler, Vern L SchrammAbstract:The expeditious convergent synthesis of the potent human Purine Nucleoside Phosphorylase inhibitor DADMe-Immucillin-G (3) was achieved via the Mannich reaction. The Mannich chemistry of a series of deazaPurines and amine hydrochlorides was also investigated.
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Exploring Structure−Activity Relationships of Transition State Analogues of Human Purine Nucleoside Phosphorylase
Journal of medicinal chemistry, 2003Co-Authors: Gary B Evans, Richard H Furneaux, Andrzej Lewandowicz, Vern L Schramm, Peter C TylerAbstract:The aza-C-Nucleosides, Immucillin-H and Immucillin-G, are transition state analogue inhibitors of Purine Nucleoside Phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2‘-, 3‘-, or 5‘-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazaPurine, as well as methylene-bridged analogues, have been synthesized and tested for their inhibition of human Purine Nucleoside Phosphorylase. All analogues were poorer inhibitors, which reflects the superior capture of transition state features in the parent immucillins.
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exploring structure activity relationships of transition state analogues of human Purine Nucleoside Phosphorylase
Journal of Medicinal Chemistry, 2003Co-Authors: Gary B Evans, Richard H Furneaux, Andrzej Lewandowicz, Vern L Schramm, Peter C TylerAbstract:The aza-C-Nucleosides, Immucillin-H and Immucillin-G, are transition state analogue inhibitors of Purine Nucleoside Phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2‘-, 3‘-, or 5‘-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazaPurine, as well as methylene-bridged analogues, have been synthesized and tested for their inhibition of human Purine Nucleoside Phosphorylase. All analogues were poorer inhibitors, which reflects the superior capture of transition state features in the parent immucillins.
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synthesis of transition state analogue inhibitors for Purine Nucleoside Phosphorylase and n riboside hydrolases
Tetrahedron, 2000Co-Authors: Gary B Evans, Richard H Furneaux, Vern L Schramm, Graeme J Gainsford, Peter C TylerAbstract:Abstract Syntheses of the ‘Immucillins’, potent aza-C-Nucleoside inhibitors of Purine Nucleoside Phosphorylase are reported as well as those of 5-deoxy-, 5-deoxyfluoro- and 2-deoxy- analogues and others having modified bases.
