作者
John Liddle,Andrew C. Pearce,Christopher C. Arico-Muendel,Svetlana Belyanskaya,A.S. Brewster,Murray J. B. Brown,Chun‐wa Chung,Alexis Denis,N Sinisa Dodic,Anthony Dossang,Peter Eddershaw,Diana Klimaszewska,Imran Ul Haq,Duncan S. Holmes,Alistair M. Jagger,Toral Jakhria,Émilie Jigorel,Ken Lind,Jeff Messer,Margaret Neu,Allison Olszewski,Riccardo Ronzoni,James E. Rowedder,Martin Rüdiger,Steve Skinner,Kathrine J. Smith,Lionel Trottet,Iain Uings,Zhengrong Zhu,James A. Irving,David A. Lomas
摘要
α1-antitrypsin deficiency is characterised by the misfolding and intracellular polymerisation of mutant α1-antitrypsin protein within the endoplasmic reticulum (ER) of hepatocytes. Small molecules that bind and stabilise Z α1-antitrypsin were identified via a DNA-encoded library screen. A subsequent structure based optimisation led to a series of highly potent, selective and cellular active α1-antitrypsin correctors.