Structural Development Study of a Novel Pharmacological Chaperone for Folding-defective Rhodopsin Mutants Responsible for Retinitis Pigmentosa

• OHGANE Kenji

  Institute of Molecular and Cellular Biosciences, The University of Tokyo

• DODO Kosuke

  RIKEN, Advanced Science Institute (ASI)

• HASHIMOTO Yuichi

  Institute of Molecular and Cellular Biosciences, The University of Tokyo

Bibliographic Information

Other Title

• フォールディング・トラフィッキング異常の修正作用を有するリガンドの創製　～網膜色素変性症への応用を目指した変異型ロドプシンのフォールディングを促進するロドプシンリガンドの創製研究～
• フォールディング トラフィッキング イジョウ ノ シュウセイ サヨウ オ ユウスル リガンド ノ ソウセイ モウマク シキソ ヘンセイショウ エ ノ オウヨウ オ メザシタ ヘンイケイ ロドプシン ノ フォールディング オ ソクシン スル ロドプシンリガンド ノ ソウセイ ケンキュウ

Abstract

  The retinitis pigmentosa (RP)-causing mutant of rhodopsin, Pro23His (P23H) rhodopsin, is folding defective and unable to traffic beyond the endoplasmic reticulum (ER). This ER retention, and in some cases, aggregation are proposed to result in ER-stress and eventually cell death. The endogenous rhodopsin ligand 11-cis-retinal and its isomer 9-cis-retinal have been shown to act as pharmacological chaperones, promoting proper folding and trafficking of the P23H rhodopsin. In spite of this promising effect, the development of retinals and related polyenealdehydes as pharmacological agents has been hampered by their undesirable properties, which include chemical instability, photolability, and potential retinoidal actions. Here we report the design and synthesis of a class of more stable nonpolyene-type rhodopsin ligands, structurally distinct from, and with lower toxicity than, retinals. A structure-activity relationship study was conducted using cell-surface expression assay to quantify folding/trafficking efficiency of P23H rhodopsin.<br>

Journal

• YAKUGAKU ZASSHI

  YAKUGAKU ZASSHI 131 (3), 325-334, 2011

  The Pharmaceutical Society of Japan

Keywords

• pharmacological chaperone
• rhodopsin
• retinitis pigmentosa

Details

• CRID: 1390001206128610176
• NII Article ID: 130000678893
• NII Book ID: AN00284903
• DOI: 10.1248/yakushi.131.325
• COI: 1:CAS:528:DC%2BC3MXhtFGlurrN
• ISSN: 13475231
• ISSN: 00316903
• NDL BIB ID: 11032140
• PubMed: 21372525
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I11032140
• Web Site: http://www.jstage.jst.go.jp/article/yakushi/131/3/131_3_325/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2011303660
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed