2014 Fiscal Year Final Research Report
Design and synthesis of long-acting BACE1 inhibitors incorporating unnatural amino acids
| Project/Area Number |
24790117
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Drug development chemistry
|
|---|
| Research Institution | Waseda University (2013-2014)
Kogakuin University (2012) |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Keywords | アルツハイマー病 |
|---|
| Outline of Final Research Achievements |
The aspartic protease beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) has been studied for its role in Alzheimer’s disease (AD), and is known to be responsible for generating amyloid β peptides (Aβ). As insoluble Aβ plaques are considered to be critical for the onset of AD, BACE1 has been an important target for the development of therapeutic agents against AD. In a previous study, the author performed a peptide library screen and identified several unnatural amino acids that enable superior substrate cleavage by BACE1. In this study, the author has synthesized several substrate-based BACE1 inhibitors comprising unnatural amino acids that were identified in the previous screen. The enzymatic assay proved that the inhibitors displayed moderate inhibitory activity against recombinant BACE1. In addition, a further peptide library screen was carried out in positions P4-P1′ of the substrate and several unnatural amino acids were newly identified for future drug design.
|
| Free Research Field |
創薬科学分野
|
