Academia Sinica

Other

National Health Research Institutes

Kai-Fa Huang

Andrew H-j Wang

Chuan Shih

Chih-Hao Chen

Chiung-Tong Chen

Hwei-Jiung Wang

Andrew H -j Wang

Yan-Ping Shih

Benzimidazole compounds of formula (I), shown below, are disclosed. The compounds are potent human glutaminyl cyclase inhibitors. Also disclosed is a pharmaceutical composition containing one of these compounds and a pharmaceutical acceptable carrier, as well as a method of treating Alzheimer's disease or Huntington's disease by administering to a subject in need thereof an effective amount of such a compound. 

Benzimidazole compounds and use thereof for treating Alzheimer's Disease or Huntington's Disease

Disclosed herein is an expression system and uses thereof. The expression system comprises two vectors that express two fusion proteins and a glutaminyl cyclase (QC) with E45Q mutation, so as to autonomously produce a target protein having a N-terminal pyroglutamate (pGlu) residue in a host cell. The first fusion protein is composed of a maltose binding protein (MBP) and a tobacco etch virus protease (TEVP); and the second fusion protein includes in sequence, a thioredoxin, a S-tag, a linker having a TEVP recognition site therein, a target protein, and a (His)--tag. The second fusion protein is cleaved by the TEVP that is expressed by the first fusion protein, and then catalyzed by QC with E45Q mutation so as to autonomously produce the target protein having a N-terminal pGlu residue in the host cell.

Expression system for producing protein having a N-terminal pyroglutamate residue

A crystalline structure of glutaminyl cyclase (QC) is described. Also described are the methods of preparing the crystalline structure of QC and the methods for identifying candidate inhibitors of QC. In addition, a structural basis for the rational design or identification of new inhibitors that may be used to treat QC-associated disorders is also described.

Crystal structure of soluble glutaminyl cyclase

A vector for expressing a soluble glutaminyl cyclase (QC) in bacterial cells is described. The vector contains a sequence encoding a fusion QC, which has a fusion protein tag selected from a Nus protein tag or a thioredoxin (Trx) tag, a QC, and a linker having at least one (His)-tag between the QC and the fusion protein tag, in which x is an integer of at least 6. Methods for expressing a soluble glutaminyl cyclase (QC) by the vector are also described.

Express system of soluble glutaminyl cyclase

A crystalline structure of glutaminyl cyclase (QC). is described. Also described are the methods of preparing the crystalline structure of QC and the methods for identifying candidate inhibitors of QC. In addition, a structural basis for the rational design or identification of new inhibitors that may be used to treat QC-associated disorders is also described.

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Taipei, Taiwan

Kai-Fa Huang