Concentration Assay:Article Title: Inhibition of cell surface protein disulfide isomerase
Article Snippet: TABLE I COMPOUNDS THAT INDUCE L-SELECTIN SHEDDING FROM NEUTROPHILS 100% LOSS from cell surface in 10 min at 37 deg. at the approximate concentration: (membrane-impermeable inhibitors are marked with*) Thiol Blocking and Oxidizing reagents PAO −1 uM vicinal dithiol specific PAO-DNP −1 uM DNP added far from AsO group Aminophenylmercuric 10 uM monothiol reactives activates MMPs acetate Nitroblue tetrazolium 100 uM superoxide scavenger and oxidant Hydrogen peroxide 150 uM oxidant, effect inhibitable by excess DMPS Monobromobimane 100 uM thiol blocker (fluorescent as bound) mBBr Dibromobimane bBBr 100 um dithiol reactive, spacing differs from PAO *DIDS 200 uM thiol and amino-group reactive N-ethylmaleimide 250 uM thiol blocker *Quaternary 300 uM membrane-impermeable mBBr bromobimane qBBr Iodoacetate IA 300 uM thiol blocker, also depletes energy *Mersalyl acid 500 uM thiol-reactive via - HgOH Thimerosal 500 um thiol blocker, used as preservative *DTNB 1 mM thiol-blocker PMSF 1 mM attacks and blocks - SH (and OH) groups Diamide 1 mM thiol oxidizer/crosslinker, ADA analog Azodicarbonamide 1 mM blocks HIV infectivity, flour additive Iodoacetamide 10 mM thiol reagent, low efficacy (vs. IA) surprising Iodosobenzoate 1 mM A dithiol oxidizing reagent just like PAO, but with Iodine instead of arsenic, causes direct oxidation of dithiols Dithiol Reactive Ions: Arsenic (As203) 50 uM Cadmium (CdC12) 1 mM Antimony (Sb203) 50 uM Other Reagents and Conditions: *Dehydroascorbate 1 M specifically and only reduced by PDI or glutaredoxin, would lead to net oxidation of PDI Chlorpromazine 50 mM blocks HIV infectivity at this concentration Methoxychlor 50 uM a pesticide, a calmodulin antagonist DDT 50 uM a pesticide, a calmodulin antagonist Disulfiram (Antabuse) 50 uM drug that induces alcohol aversion *Thioredoxin 50 ug/ml reductant at cell surface, poor isomerase, has biphasic effect on shedding *Protein Disulfide 20 ug/ml effective isomerase at cell surface Isomerase Somatostatin 200 uM peptide PDI inhibitor UV irradiation 10 min produces ROS, effect TAPI inhibitable As alluded to supra, the inhibitors of the invention are especially useful in vivo for blocking entry of virions into targeted host cells by blocking an essential PDI-mediated step of their transmembrane process.
Membrane:Article Title: Inhibition of cell surface protein disulfide isomerase
Article Snippet: TABLE I COMPOUNDS THAT INDUCE L-SELECTIN SHEDDING FROM NEUTROPHILS 100% LOSS from cell surface in 10 min at 37 deg. at the approximate concentration: (membrane-impermeable inhibitors are marked with*) Thiol Blocking and Oxidizing reagents PAO −1 uM vicinal dithiol specific PAO-DNP −1 uM DNP added far from AsO group Aminophenylmercuric 10 uM monothiol reactives activates MMPs acetate Nitroblue tetrazolium 100 uM superoxide scavenger and oxidant Hydrogen peroxide 150 uM oxidant, effect inhibitable by excess DMPS Monobromobimane 100 uM thiol blocker (fluorescent as bound) mBBr Dibromobimane bBBr 100 um dithiol reactive, spacing differs from PAO *DIDS 200 uM thiol and amino-group reactive N-ethylmaleimide 250 uM thiol blocker *Quaternary 300 uM membrane-impermeable mBBr bromobimane qBBr Iodoacetate IA 300 uM thiol blocker, also depletes energy *Mersalyl acid 500 uM thiol-reactive via - HgOH Thimerosal 500 um thiol blocker, used as preservative *DTNB 1 mM thiol-blocker PMSF 1 mM attacks and blocks - SH (and OH) groups Diamide 1 mM thiol oxidizer/crosslinker, ADA analog Azodicarbonamide 1 mM blocks HIV infectivity, flour additive Iodoacetamide 10 mM thiol reagent, low efficacy (vs. IA) surprising Iodosobenzoate 1 mM A dithiol oxidizing reagent just like PAO, but with Iodine instead of arsenic, causes direct oxidation of dithiols Dithiol Reactive Ions: Arsenic (As203) 50 uM Cadmium (CdC12) 1 mM Antimony (Sb203) 50 uM Other Reagents and Conditions: *Dehydroascorbate 1 M specifically and only reduced by PDI or glutaredoxin, would lead to net oxidation of PDI Chlorpromazine 50 mM blocks HIV infectivity at this concentration Methoxychlor 50 uM a pesticide, a calmodulin antagonist DDT 50 uM a pesticide, a calmodulin antagonist Disulfiram (Antabuse) 50 uM drug that induces alcohol aversion *Thioredoxin 50 ug/ml reductant at cell surface, poor isomerase, has biphasic effect on shedding *Protein Disulfide 20 ug/ml effective isomerase at cell surface Isomerase Somatostatin 200 uM peptide PDI inhibitor UV irradiation 10 min produces ROS, effect TAPI inhibitable As alluded to supra, the inhibitors of the invention are especially useful in vivo for blocking entry of virions into targeted host cells by blocking an essential PDI-mediated step of their transmembrane process.
Blocking Assay:Article Title: Inhibition of cell surface protein disulfide isomerase
Article Snippet: TABLE I COMPOUNDS THAT INDUCE L-SELECTIN SHEDDING FROM NEUTROPHILS 100% LOSS from cell surface in 10 min at 37 deg. at the approximate concentration: (membrane-impermeable inhibitors are marked with*) Thiol Blocking and Oxidizing reagents PAO −1 uM vicinal dithiol specific PAO-DNP −1 uM DNP added far from AsO group Aminophenylmercuric 10 uM monothiol reactives activates MMPs acetate Nitroblue tetrazolium 100 uM superoxide scavenger and oxidant Hydrogen peroxide 150 uM oxidant, effect inhibitable by excess DMPS Monobromobimane 100 uM thiol blocker (fluorescent as bound) mBBr Dibromobimane bBBr 100 um dithiol reactive, spacing differs from PAO *DIDS 200 uM thiol and amino-group reactive N-ethylmaleimide 250 uM thiol blocker *Quaternary 300 uM membrane-impermeable mBBr bromobimane qBBr Iodoacetate IA 300 uM thiol blocker, also depletes energy *Mersalyl acid 500 uM thiol-reactive via - HgOH Thimerosal 500 um thiol blocker, used as preservative *DTNB 1 mM thiol-blocker PMSF 1 mM attacks and blocks - SH (and OH) groups Diamide 1 mM thiol oxidizer/crosslinker, ADA analog Azodicarbonamide 1 mM blocks HIV infectivity, flour additive Iodoacetamide 10 mM thiol reagent, low efficacy (vs. IA) surprising Iodosobenzoate 1 mM A dithiol oxidizing reagent just like PAO, but with Iodine instead of arsenic, causes direct oxidation of dithiols Dithiol Reactive Ions: Arsenic (As203) 50 uM Cadmium (CdC12) 1 mM Antimony (Sb203) 50 uM Other Reagents and Conditions: *Dehydroascorbate 1 M specifically and only reduced by PDI or glutaredoxin, would lead to net oxidation of PDI Chlorpromazine 50 mM blocks HIV infectivity at this concentration Methoxychlor 50 uM a pesticide, a calmodulin antagonist DDT 50 uM a pesticide, a calmodulin antagonist Disulfiram (Antabuse) 50 uM drug that induces alcohol aversion *Thioredoxin 50 ug/ml reductant at cell surface, poor isomerase, has biphasic effect on shedding *Protein Disulfide 20 ug/ml effective isomerase at cell surface Isomerase Somatostatin 200 uM peptide PDI inhibitor UV irradiation 10 min produces ROS, effect TAPI inhibitable As alluded to supra, the inhibitors of the invention are especially useful in vivo for blocking entry of virions into targeted host cells by blocking an essential PDI-mediated step of their transmembrane process.
Infection:Article Title: Inhibition of cell surface protein disulfide isomerase
Article Snippet: TABLE I COMPOUNDS THAT INDUCE L-SELECTIN SHEDDING FROM NEUTROPHILS 100% LOSS from cell surface in 10 min at 37 deg. at the approximate concentration: (membrane-impermeable inhibitors are marked with*) Thiol Blocking and Oxidizing reagents PAO −1 uM vicinal dithiol specific PAO-DNP −1 uM DNP added far from AsO group Aminophenylmercuric 10 uM monothiol reactives activates MMPs acetate Nitroblue tetrazolium 100 uM superoxide scavenger and oxidant Hydrogen peroxide 150 uM oxidant, effect inhibitable by excess DMPS Monobromobimane 100 uM thiol blocker (fluorescent as bound) mBBr Dibromobimane bBBr 100 um dithiol reactive, spacing differs from PAO *DIDS 200 uM thiol and amino-group reactive N-ethylmaleimide 250 uM thiol blocker *Quaternary 300 uM membrane-impermeable mBBr bromobimane qBBr Iodoacetate IA 300 uM thiol blocker, also depletes energy *Mersalyl acid 500 uM thiol-reactive via - HgOH Thimerosal 500 um thiol blocker, used as preservative *DTNB 1 mM thiol-blocker PMSF 1 mM attacks and blocks - SH (and OH) groups Diamide 1 mM thiol oxidizer/crosslinker, ADA analog Azodicarbonamide 1 mM blocks HIV infectivity, flour additive Iodoacetamide 10 mM thiol reagent, low efficacy (vs. IA) surprising Iodosobenzoate 1 mM A dithiol oxidizing reagent just like PAO, but with Iodine instead of arsenic, causes direct oxidation of dithiols Dithiol Reactive Ions: Arsenic (As203) 50 uM Cadmium (CdC12) 1 mM Antimony (Sb203) 50 uM Other Reagents and Conditions: *Dehydroascorbate 1 M specifically and only reduced by PDI or glutaredoxin, would lead to net oxidation of PDI Chlorpromazine 50 mM blocks HIV infectivity at this concentration Methoxychlor 50 uM a pesticide, a calmodulin antagonist DDT 50 uM a pesticide, a calmodulin antagonist Disulfiram (Antabuse) 50 uM drug that induces alcohol aversion *Thioredoxin 50 ug/ml reductant at cell surface, poor isomerase, has biphasic effect on shedding *Protein Disulfide 20 ug/ml effective isomerase at cell surface Isomerase Somatostatin 200 uM peptide PDI inhibitor UV irradiation 10 min produces ROS, effect TAPI inhibitable As alluded to supra, the inhibitors of the invention are especially useful in vivo for blocking entry of virions into targeted host cells by blocking an essential PDI-mediated step of their transmembrane process.
Irradiation:Article Title: Inhibition of cell surface protein disulfide isomerase
Article Snippet: TABLE I COMPOUNDS THAT INDUCE L-SELECTIN SHEDDING FROM NEUTROPHILS 100% LOSS from cell surface in 10 min at 37 deg. at the approximate concentration: (membrane-impermeable inhibitors are marked with*) Thiol Blocking and Oxidizing reagents PAO −1 uM vicinal dithiol specific PAO-DNP −1 uM DNP added far from AsO group Aminophenylmercuric 10 uM monothiol reactives activates MMPs acetate Nitroblue tetrazolium 100 uM superoxide scavenger and oxidant Hydrogen peroxide 150 uM oxidant, effect inhibitable by excess DMPS Monobromobimane 100 uM thiol blocker (fluorescent as bound) mBBr Dibromobimane bBBr 100 um dithiol reactive, spacing differs from PAO *DIDS 200 uM thiol and amino-group reactive N-ethylmaleimide 250 uM thiol blocker *Quaternary 300 uM membrane-impermeable mBBr bromobimane qBBr Iodoacetate IA 300 uM thiol blocker, also depletes energy *Mersalyl acid 500 uM thiol-reactive via - HgOH Thimerosal 500 um thiol blocker, used as preservative *DTNB 1 mM thiol-blocker PMSF 1 mM attacks and blocks - SH (and OH) groups Diamide 1 mM thiol oxidizer/crosslinker, ADA analog Azodicarbonamide 1 mM blocks HIV infectivity, flour additive Iodoacetamide 10 mM thiol reagent, low efficacy (vs. IA) surprising Iodosobenzoate 1 mM A dithiol oxidizing reagent just like PAO, but with Iodine instead of arsenic, causes direct oxidation of dithiols Dithiol Reactive Ions: Arsenic (As203) 50 uM Cadmium (CdC12) 1 mM Antimony (Sb203) 50 uM Other Reagents and Conditions: *Dehydroascorbate 1 M specifically and only reduced by PDI or glutaredoxin, would lead to net oxidation of PDI Chlorpromazine 50 mM blocks HIV infectivity at this concentration Methoxychlor 50 uM a pesticide, a calmodulin antagonist DDT 50 uM a pesticide, a calmodulin antagonist Disulfiram (Antabuse) 50 uM drug that induces alcohol aversion *Thioredoxin 50 ug/ml reductant at cell surface, poor isomerase, has biphasic effect on shedding *Protein Disulfide 20 ug/ml effective isomerase at cell surface Isomerase Somatostatin 200 uM peptide PDI inhibitor UV irradiation 10 min produces ROS, effect TAPI inhibitable As alluded to supra, the inhibitors of the invention are especially useful in vivo for blocking entry of virions into targeted host cells by blocking an essential PDI-mediated step of their transmembrane process.
In Vivo:Article Title: Inhibition of cell surface protein disulfide isomerase
Article Snippet: TABLE I COMPOUNDS THAT INDUCE L-SELECTIN SHEDDING FROM NEUTROPHILS 100% LOSS from cell surface in 10 min at 37 deg. at the approximate concentration: (membrane-impermeable inhibitors are marked with*) Thiol Blocking and Oxidizing reagents PAO −1 uM vicinal dithiol specific PAO-DNP −1 uM DNP added far from AsO group Aminophenylmercuric 10 uM monothiol reactives activates MMPs acetate Nitroblue tetrazolium 100 uM superoxide scavenger and oxidant Hydrogen peroxide 150 uM oxidant, effect inhibitable by excess DMPS Monobromobimane 100 uM thiol blocker (fluorescent as bound) mBBr Dibromobimane bBBr 100 um dithiol reactive, spacing differs from PAO *DIDS 200 uM thiol and amino-group reactive N-ethylmaleimide 250 uM thiol blocker *Quaternary 300 uM membrane-impermeable mBBr bromobimane qBBr Iodoacetate IA 300 uM thiol blocker, also depletes energy *Mersalyl acid 500 uM thiol-reactive via - HgOH Thimerosal 500 um thiol blocker, used as preservative *DTNB 1 mM thiol-blocker PMSF 1 mM attacks and blocks - SH (and OH) groups Diamide 1 mM thiol oxidizer/crosslinker, ADA analog Azodicarbonamide 1 mM blocks HIV infectivity, flour additive Iodoacetamide 10 mM thiol reagent, low efficacy (vs. IA) surprising Iodosobenzoate 1 mM A dithiol oxidizing reagent just like PAO, but with Iodine instead of arsenic, causes direct oxidation of dithiols Dithiol Reactive Ions: Arsenic (As203) 50 uM Cadmium (CdC12) 1 mM Antimony (Sb203) 50 uM Other Reagents and Conditions: *Dehydroascorbate 1 M specifically and only reduced by PDI or glutaredoxin, would lead to net oxidation of PDI Chlorpromazine 50 mM blocks HIV infectivity at this concentration Methoxychlor 50 uM a pesticide, a calmodulin antagonist DDT 50 uM a pesticide, a calmodulin antagonist Disulfiram (Antabuse) 50 uM drug that induces alcohol aversion *Thioredoxin 50 ug/ml reductant at cell surface, poor isomerase, has biphasic effect on shedding *Protein Disulfide 20 ug/ml effective isomerase at cell surface Isomerase Somatostatin 200 uM peptide PDI inhibitor UV irradiation 10 min produces ROS, effect TAPI inhibitable As alluded to supra, the inhibitors of the invention are especially useful in vivo for blocking entry of virions into targeted host cells by blocking an essential PDI-mediated step of their transmembrane process.
Positive Control:Article Title: Inhibition of cell surface protein disulfide isomerase
Article Snippet: TABLE I COMPOUNDS THAT INDUCE L-SELECTIN SHEDDING FROM NEUTROPHILS 100% LOSS from cell surface in 10 min at 37 deg. at the approximate concentration: (membrane-impermeable inhibitors are marked with*) Thiol Blocking and Oxidizing reagents PAO −1 uM vicinal dithiol specific PAO-DNP −1 uM DNP added far from AsO group Aminophenylmercuric 10 uM monothiol reactives activates MMPs acetate Nitroblue tetrazolium 100 uM superoxide scavenger and oxidant Hydrogen peroxide 150 uM oxidant, effect inhibitable by excess DMPS Monobromobimane 100 uM thiol blocker (fluorescent as bound) mBBr Dibromobimane bBBr 100 um dithiol reactive, spacing differs from PAO *DIDS 200 uM thiol and amino-group reactive N-ethylmaleimide 250 uM thiol blocker *Quaternary 300 uM membrane-impermeable mBBr bromobimane qBBr Iodoacetate IA 300 uM thiol blocker, also depletes energy *Mersalyl acid 500 uM thiol-reactive via - HgOH Thimerosal 500 um thiol blocker, used as preservative *DTNB 1 mM thiol-blocker PMSF 1 mM attacks and blocks - SH (and OH) groups Diamide 1 mM thiol oxidizer/crosslinker, ADA analog Azodicarbonamide 1 mM blocks HIV infectivity, flour additive Iodoacetamide 10 mM thiol reagent, low efficacy (vs. IA) surprising Iodosobenzoate 1 mM A dithiol oxidizing reagent just like PAO, but with Iodine instead of arsenic, causes direct oxidation of dithiols Dithiol Reactive Ions: Arsenic (As203) 50 uM Cadmium (CdC12) 1 mM Antimony (Sb203) 50 uM Other Reagents and Conditions: *Dehydroascorbate 1 M specifically and only reduced by PDI or glutaredoxin, would lead to net oxidation of PDI Chlorpromazine 50 mM blocks HIV infectivity at this concentration Methoxychlor 50 uM a pesticide, a calmodulin antagonist DDT 50 uM a pesticide, a calmodulin antagonist Disulfiram (Antabuse) 50 uM drug that induces alcohol aversion *Thioredoxin 50 ug/ml reductant at cell surface, poor isomerase, has biphasic effect on shedding *Protein Disulfide 20 ug/ml effective isomerase at cell surface Isomerase Somatostatin 200 uM peptide PDI inhibitor UV irradiation 10 min produces ROS, effect TAPI inhibitable As alluded to supra, the inhibitors of the invention are especially useful in vivo for blocking entry of virions into targeted host cells by blocking an essential PDI-mediated step of their transmembrane process.
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