Selection of Human Metalloantibodies from a Combinatorial Phage Single-Chain Antibody Library

1999 ◽  
Vol 121 (27) ◽  
pp. 6517-6518 ◽  
Author(s):  
Changshou Gao ◽  
Oliver Brümmer ◽  
Shenlan Mao ◽  
Kim D. Janda



2016 ◽  
Vol 58 (12) ◽  
pp. 1264-1269 ◽  
Author(s):  
Guang-Hui Zhang ◽  
Li Li ◽  
Changfu Hao ◽  
Jing-Chao Ren ◽  
Hongyi Zhang ◽  
...  


2019 ◽  
Vol 27 (1) ◽  
pp. 21-34 ◽  
Author(s):  
Sepideh Jalilzadeh-Razin ◽  
Malihe Mantegi ◽  
Mohammad R. Tohidkia ◽  
Yaghub Pazhang ◽  
Mohammad M. Pourseif ◽  
...  


2017 ◽  
Vol 114 (25) ◽  
pp. 6444-6449 ◽  
Author(s):  
Anna Munke ◽  
Jonas Persson ◽  
Tanja Weiffert ◽  
Erwin De Genst ◽  
Georg Meisl ◽  
...  

The aggregation of the amyloid β peptide (Aβ) into amyloid fibrils is a defining characteristic of Alzheimer’s disease. Because of the complexity of this aggregation process, effective therapeutic inhibitors will need to target the specific microscopic steps that lead to the production of neurotoxic species. We introduce a strategy for generating fibril-specific antibodies that selectively suppress fibril-dependent secondary nucleation of the 42-residue form of Aβ (Aβ42). We target this step because it has been shown to produce the majority of neurotoxic species during aggregation of Aβ42. Starting from large phage display libraries of single-chain antibody fragments (scFvs), the three-stage approach that we describe includes (i) selection of scFvs with high affinity for Aβ42 fibrils after removal of scFvs that bind Aβ42 in its monomeric form; (ii) ranking, by surface plasmon resonance affinity measurements, of the resulting candidate scFvs that bind to the Aβ42 fibrils; and (iii) kinetic screening and analysis to find the scFvs that inhibit selectively the fibril-catalyzed secondary nucleation process in Aβ42 aggregation. By applying this approach, we have identified four scFvs that inhibit specifically the fibril-dependent secondary nucleation process. Our method also makes it possible to discard antibodies that inhibit elongation, an important factor because the suppression of elongation does not target directly the production of toxic oligomers and may even lead to its increase. On the basis of our results, we suggest that the method described here could form the basis for rationally designed immunotherapy strategies to combat Alzheimer’s and related neurodegenerative diseases.



1996 ◽  
Vol 271 (26) ◽  
pp. 15682-15686 ◽  
Author(s):  
Ying Tang ◽  
Ning Jiang ◽  
Cushrow Parakh ◽  
Donald Hilvert


IUBMB Life ◽  
1999 ◽  
Vol 48 (5) ◽  
pp. 513-517 ◽  
Author(s):  
Xinsheng Gao ◽  
Yixiu Huang ◽  
Shenggeng Zhu


2010 ◽  
Vol 9 (7) ◽  
pp. 1449-1460 ◽  
Author(s):  
Arturo B. Ramirez ◽  
Christian M. Loch ◽  
Yuzheng Zhang ◽  
Yan Liu ◽  
Xiaohong Wang ◽  
...  


IUBMB Life ◽  
1999 ◽  
Vol 48 (5) ◽  
pp. 513-517
Author(s):  
Xinsheng Gao ◽  
Yixiu Huang ◽  
Shenggeng Zhu


Sign in / Sign up

Export Citation Format

Share Document