2013 Fiscal Year Final Research Report
Development of neo-biologics targeted on protein-protein interaction sites
| Project/Area Number |
23390140
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Applied pharmacology
|
|---|
| Research Institution | The University of Tokushima |
|---|
Principal Investigator |
ITOH Kohji 徳島大学, ヘルスバイオサイエンス研究部, 教授 (00184656)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HIROKAWA Takatsugu 産業技術総合研究所, 生命情報工学研究センター, 研究チーム長 (20357867)
|
|---|
| Project Period (FY) |
2011-04-01 – 2014-03-31
|
| Keywords | リソソーム酵素 / 酵素補充療法 / ケミカルシャペロン / 疾患特異的iPS細胞 / 酵素増強薬 / リソソーム病 / in silicoデザイン / トランスジェニックカイコ |
|---|
| Research Abstract |
To develop novel therapeutics for human deficiencies (lysosomal storage diseases) of lysosomal cathepsin A (CathA) and neuraminidase-1 (NEU1) based on protein-protein interaction between CathA and NEU1, we produced transgenic (Tg) silkworm strains overexpressing human CathA and NEU1 in middle silk glands, and succeeded in purification and elucidation of X-ray crystal structure of the enzymatically active CathA. The conjugates of active CathA purified from Tg silk glands and cell-penetrating peptides (R8) had replacement effects on cultured fibroblasts derived from patients with CathA deficiency (Galactosialidosis) to reduce the accumulated sialyloligosaccharides. In addition, siastatin B was found to have stabilizing effects like a chaperone compound on recombinant human cytosolic NEU2 with structural similarity to NEU1.
|
