Details

Autor(en) / Beteiligte

• Swift, Joseph
• Saing, Sopany
• Rouet, Romain
• Dudgeon, Kip
• Schofield, Peter
• Sewell, William
• Christ, Daniel

Titel

Identification of aggregation inhibitors of the human antibody light chain repertoire by phage display

Ist Teil von

• Protein engineering, design and selection, 2014-10, Vol.27 (10), p.405-409

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2014

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Protein aggregation hinders the development of biologics and underpins the molecular basis of many human diseases. Considerable variation of aggregation propensity exists not only between different proteins, but also within a single homologous family, which complicates analyses. A classic example is observed among human antibody light chains, which aggregate in a clonally specific manner, driven by sequence diversity within their variable domains. Here, we utilise a library versus library strategy, based on phage display and a chemical library of FDA approved drugs, to overcome this limitation. Our approach allowed the identification of small molecule drugs that inhibit the aggregation of the human light chain repertoire. It also provides a general template for the small molecule targeting of diverse protein families.