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PMC:7594251 / 42214-44525 JSONTXT 7 Projects

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Id Subject Object Predicate Lexical cue
T293 0-6 Sentence denotes 3.1.1.
T294 7-29 Sentence denotes Target Based Screening
T295 30-168 Sentence denotes Target based screening typically utilizes the “SAR by NMR” (structure-activity-relationship by nuclear magnetic resonance) approach [246].
T296 169-253 Sentence denotes SAR is primarily used to identify and develop extremely tight-binding ligands [247].
T297 254-449 Sentence denotes 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].
T298 450-534 Sentence denotes Multiple spectra for the target are recorded in the presence and absence of ligands.
T299 535-697 Sentence denotes The binding ligand will cause chemical shift perturbations in the target, and these perturbations are often easily visualized by overlaying the two spectra [247].
T300 698-832 Sentence denotes For example Hajduk et al. investigated the binding interactions of 2-phenylimidazole with the FKBP protein as shown in Figure 7 [249].
T301 833-1042 Sentence denotes From 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].
T302 1043-1286 Sentence denotes 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.
T303 1287-1428 Sentence denotes Several examples of the successful applications of SAR by NMR in drug design research are replete in the scientific literature [204,251,252].
T304 1429-1609 Sentence denotes SAR 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].
T305 1610-1706 Sentence denotes It works particularly well for targeting proteins with adjacent “subpocket” binding sites [248].
T306 1707-1806 Sentence denotes Furthermore, SAR by NMR is cost-effective when combined with HTS (High Throughput Screening) [255].
T307 1807-1982 Sentence denotes 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].
T308 1983-2311 Sentence denotes 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].