[Studies on Functional Molecules Based on Peptide Chemistry].
Yakugaku Zasshi
; 141(2): 215-233, 2021.
Article
in Japanese
| MEDLINE | ID: covidwho-1055838
ABSTRACT
Studies on functional molecules starting from syntheses of cysteine-containing peptides and protein are described. Starting from evaluation of a cysteine specific side-reaction, a specific reaction for disulfide-bond formation was developed. The reaction made it possible to independently construct a disulfide bridge without effecting the existing disulfide bonds, which resulted in a unique approach for the synthesis of human insulin by site-specific disulfide bond formation. In a series of studies on sulfur-containing amino acids, another cysteine related un-natural amino acid, α-methyl cysteine, was used for the total syntheses of natural products containing a unique thiazorine/thiazole ring system. Chloroimidazolidium coupling reagent developed by us was effective for the successive couplings of the α-methyl cysteine residues. Based on these synthetic studies, design and evaluation of protease inhibitors were then studied, since a stereo-specific synthesis of the key structure is crucial to make the inhibitor an effective functional molecule in the interactions with its target protease. As the target proteases, ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) and chymotrypsin-like protease of severe acute respiratory syndrome (SARS 3CL protease) were selected the former is a crucial enzyme for amyloid ß production and the latter is an essential enzyme for the re-construction of SARS corona virus in host cells. Structure optimization procedure of the respective inhibitors are described based on X-ray crystal structure analyses of the inhibitor-protease complex.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Peptides
/
Amino Acids
Type of study:
Experimental Studies
Language:
Japanese
Journal:
Yakugaku Zasshi
Year:
2021
Document Type:
Article
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