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LitCovid-PD-FMA-UBERON

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T84514","span":{"begin":797,"end":804},"obj":"Body_part"},{"id":"T31879","span":{"begin":1651,"end":1659},"obj":"Body_part"}],"attributes":[{"id":"A72773","pred":"fma_id","subj":"T84514","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A72739","pred":"fma_id","subj":"T31879","obj":"http://purl.org/sig/ont/fma/fma67257"}],"text":"3.1.1. Target Based Screening\nTarget based screening typically utilizes the “SAR by NMR” (structure-activity-relationship by nuclear magnetic resonance) approach [246]. SAR is primarily used to identify and develop extremely tight-binding ligands [247]. The ligand to target binding is traditionally monitored via chemical shift changes [247] using a correlation spectroscopy such as 1H-15N HSQC starting with the target and no ligand present [248]. Multiple spectra for the target are recorded in the presence and absence of ligands. The binding ligand will cause chemical shift perturbations in the target, and these perturbations are often easily visualized by overlaying the two spectra [247]. For example Hajduk et al. investigated the binding interactions of 2-phenylimidazole with the FKBP protein as shown in Figure 7 [249].\nFrom the overlaid spectra, chemical shift changes are measured, and from the molecular location, extent, and rate of the chemical shift changes, the binding site and affinity of the ligand is calculated [250]. Then, by following a procedure completely analogous to that of FBDD (see Figure 6), a ligand developed from multiple fragments can be optimized for the binding site of interest, again by monitoring the changes in chemical shifts of the target. Several examples of the successful applications of SAR by NMR in drug design research are replete in the scientific literature [204,251,252].\nSAR by NMR spectroscopy allows researchers to observe directly ligand binding [247] in both solution state and solid-state spectra [253], increasing the method’s versatility [254]. It works particularly well for targeting proteins with adjacent “subpocket” binding sites [248]. Furthermore, SAR by NMR is cost-effective when combined with HTS (High Throughput Screening) [255]. SAR by NMR can also be used even when atomic peak assignments in spectra are unknown, though it is much more powerful when the resonance frequency of each atom is known [254]. The main limitation of SAR by NMR, however, is its inability to distinguish between multiple binding modes (i.e., cleavage of covalent bonds or allosteric changes), and if multiple binding modes are present, it can be difficult to pinpoint the “true” binding site of the ligand solely using data obtained using SAR by NMR [254]."}

LitCovid-PD-MONDO

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T33","span":{"begin":1768,"end":1771},"obj":"Disease"}],"attributes":[{"id":"A33","pred":"mondo_id","subj":"T33","obj":"http://purl.obolibrary.org/obo/MONDO_0011549"}],"text":"3.1.1. Target Based Screening\nTarget based screening typically utilizes the “SAR by NMR” (structure-activity-relationship by nuclear magnetic resonance) approach [246]. SAR is primarily used to identify and develop extremely tight-binding ligands [247]. The ligand to target binding is traditionally monitored via chemical shift changes [247] using a correlation spectroscopy such as 1H-15N HSQC starting with the target and no ligand present [248]. Multiple spectra for the target are recorded in the presence and absence of ligands. The binding ligand will cause chemical shift perturbations in the target, and these perturbations are often easily visualized by overlaying the two spectra [247]. For example Hajduk et al. investigated the binding interactions of 2-phenylimidazole with the FKBP protein as shown in Figure 7 [249].\nFrom the overlaid spectra, chemical shift changes are measured, and from the molecular location, extent, and rate of the chemical shift changes, the binding site and affinity of the ligand is calculated [250]. Then, by following a procedure completely analogous to that of FBDD (see Figure 6), a ligand developed from multiple fragments can be optimized for the binding site of interest, again by monitoring the changes in chemical shifts of the target. Several examples of the successful applications of SAR by NMR in drug design research are replete in the scientific literature [204,251,252].\nSAR by NMR spectroscopy allows researchers to observe directly ligand binding [247] in both solution state and solid-state spectra [253], increasing the method’s versatility [254]. It works particularly well for targeting proteins with adjacent “subpocket” binding sites [248]. Furthermore, SAR by NMR is cost-effective when combined with HTS (High Throughput Screening) [255]. SAR by NMR can also be used even when atomic peak assignments in spectra are unknown, though it is much more powerful when the resonance frequency of each atom is known [254]. The main limitation of SAR by NMR, however, is its inability to distinguish between multiple binding modes (i.e., cleavage of covalent bonds or allosteric changes), and if multiple binding modes are present, it can be difficult to pinpoint the “true” binding site of the ligand solely using data obtained using SAR by NMR [254]."}

LitCovid-PD-CLO

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T299","span":{"begin":100,"end":108},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T300","span":{"begin":215,"end":224},"obj":"http://www.ebi.ac.uk/efo/EFO_0000876"},{"id":"T301","span":{"begin":349,"end":350},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T302","span":{"begin":1062,"end":1063},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T303","span":{"begin":1127,"end":1128},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"}],"text":"3.1.1. Target Based Screening\nTarget based screening typically utilizes the “SAR by NMR” (structure-activity-relationship by nuclear magnetic resonance) approach [246]. SAR is primarily used to identify and develop extremely tight-binding ligands [247]. The ligand to target binding is traditionally monitored via chemical shift changes [247] using a correlation spectroscopy such as 1H-15N HSQC starting with the target and no ligand present [248]. Multiple spectra for the target are recorded in the presence and absence of ligands. The binding ligand will cause chemical shift perturbations in the target, and these perturbations are often easily visualized by overlaying the two spectra [247]. For example Hajduk et al. investigated the binding interactions of 2-phenylimidazole with the FKBP protein as shown in Figure 7 [249].\nFrom the overlaid spectra, chemical shift changes are measured, and from the molecular location, extent, and rate of the chemical shift changes, the binding site and affinity of the ligand is calculated [250]. Then, by following a procedure completely analogous to that of FBDD (see Figure 6), a ligand developed from multiple fragments can be optimized for the binding site of interest, again by monitoring the changes in chemical shifts of the target. Several examples of the successful applications of SAR by NMR in drug design research are replete in the scientific literature [204,251,252].\nSAR by NMR spectroscopy allows researchers to observe directly ligand binding [247] in both solution state and solid-state spectra [253], increasing the method’s versatility [254]. It works particularly well for targeting proteins with adjacent “subpocket” binding sites [248]. Furthermore, SAR by NMR is cost-effective when combined with HTS (High Throughput Screening) [255]. SAR by NMR can also be used even when atomic peak assignments in spectra are unknown, though it is much more powerful when the resonance frequency of each atom is known [254]. The main limitation of SAR by NMR, however, is its inability to distinguish between multiple binding modes (i.e., cleavage of covalent bonds or allosteric changes), and if multiple binding modes are present, it can be difficult to pinpoint the “true” binding site of the ligand solely using data obtained using SAR by NMR [254]."}

LitCovid-PD-CHEBI

LitCovid-PubTator

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T293","span":{"begin":0,"end":6},"obj":"Sentence"},{"id":"T294","span":{"begin":7,"end":29},"obj":"Sentence"},{"id":"T295","span":{"begin":30,"end":168},"obj":"Sentence"},{"id":"T296","span":{"begin":169,"end":253},"obj":"Sentence"},{"id":"T297","span":{"begin":254,"end":449},"obj":"Sentence"},{"id":"T298","span":{"begin":450,"end":534},"obj":"Sentence"},{"id":"T299","span":{"begin":535,"end":697},"obj":"Sentence"},{"id":"T300","span":{"begin":698,"end":832},"obj":"Sentence"},{"id":"T301","span":{"begin":833,"end":1042},"obj":"Sentence"},{"id":"T302","span":{"begin":1043,"end":1286},"obj":"Sentence"},{"id":"T303","span":{"begin":1287,"end":1428},"obj":"Sentence"},{"id":"T304","span":{"begin":1429,"end":1609},"obj":"Sentence"},{"id":"T305","span":{"begin":1610,"end":1706},"obj":"Sentence"},{"id":"T306","span":{"begin":1707,"end":1806},"obj":"Sentence"},{"id":"T307","span":{"begin":1807,"end":1982},"obj":"Sentence"},{"id":"T308","span":{"begin":1983,"end":2311},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"3.1.1. Target Based Screening\nTarget based screening typically utilizes the “SAR by NMR” (structure-activity-relationship by nuclear magnetic resonance) approach [246]. SAR is primarily used to identify and develop extremely tight-binding ligands [247]. The ligand to target binding is traditionally monitored via chemical shift changes [247] using a correlation spectroscopy such as 1H-15N HSQC starting with the target and no ligand present [248]. Multiple spectra for the target are recorded in the presence and absence of ligands. The binding ligand will cause chemical shift perturbations in the target, and these perturbations are often easily visualized by overlaying the two spectra [247]. For example Hajduk et al. investigated the binding interactions of 2-phenylimidazole with the FKBP protein as shown in Figure 7 [249].\nFrom the overlaid spectra, chemical shift changes are measured, and from the molecular location, extent, and rate of the chemical shift changes, the binding site and affinity of the ligand is calculated [250]. Then, by following a procedure completely analogous to that of FBDD (see Figure 6), a ligand developed from multiple fragments can be optimized for the binding site of interest, again by monitoring the changes in chemical shifts of the target. Several examples of the successful applications of SAR by NMR in drug design research are replete in the scientific literature [204,251,252].\nSAR by NMR spectroscopy allows researchers to observe directly ligand binding [247] in both solution state and solid-state spectra [253], increasing the method’s versatility [254]. It works particularly well for targeting proteins with adjacent “subpocket” binding sites [248]. Furthermore, SAR by NMR is cost-effective when combined with HTS (High Throughput Screening) [255]. SAR by NMR can also be used even when atomic peak assignments in spectra are unknown, though it is much more powerful when the resonance frequency of each atom is known [254]. The main limitation of SAR by NMR, however, is its inability to distinguish between multiple binding modes (i.e., cleavage of covalent bonds or allosteric changes), and if multiple binding modes are present, it can be difficult to pinpoint the “true” binding site of the ligand solely using data obtained using SAR by NMR [254]."}