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. |