PMC:7594251 / 6073-7671 JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
T45 0-155 Sentence denotes In addition to the advantages provided by NMR, it is often used with complementary methods such as X-ray crystallography, HPLC, and mass spectrometry [69].
T46 156-363 Sentence denotes An example of this is found in work by Wyss et al. [36], where they combined X-ray crystallography with NMR fragment-based screening to create the first inhibitor candidate for BACE-1 in Alzheimer’s disease.
T47 364-549 Sentence denotes BACE-1 is a membrane-anchored aspartic acid protease and is responsible for the production of amyloid beta peptides in neurons related to the progression of Alzheimer’s disease [36,70].
T48 550-764 Sentence denotes Using NMR fragment-based screening, Wyss et al. identified isothiourea as binding to BACE-1 and confirmed this observation with the X-ray crystal structure of the complex of a ligand-efficient isothiourea fragment.
T49 765-914 Sentence denotes Information obtained from these experiments aided in design optimization, resulting in the selection of iminopyrimidinones as BACE-1 inhibitors [36].
T50 915-1013 Sentence denotes This is a perfect example of using different complementary methods to maximize scientific outcome.
T51 1014-1111 Sentence denotes However, in order to be efficient, one must know the advantages and disadvantages of each method.
T52 1112-1236 Sentence denotes One of the major issues regarding NMR is the effective size restriction when measuring targets such as proteins above 40kDa.
T53 1237-1440 Sentence denotes Recent progress has extended this mass limit; an example of this is the resolved structure of chaperone SecB in complex with unstructured proPhoA (PDB ID 5JTL) with a total mass of 119kDa using NMR [71].
T54 1441-1598 Sentence denotes In this review, we present practical guideline to use NMR techniques in drug design studies and provide examples of the successful use of NMR in drug-design.