Crystal structure reveals conservation of amyloid-β conformation recognized by 3D6 following humanization to bapineuzumab.

ABSTRACT:

Introduction

Immunotherapy targeting amyloid-β peptide is under active clinical investigation for treatment of Alzheimer's disease (AD). Among the hypotheses being investigated for impact on clinical outcome are the preferred epitope or conformation of amyloid-β to target for treatment, and the mechanism of action underlying immunotherapy. Bapineuzumab (humanized 3D6), a neo-epitope specific antibody recognizing amyloid-β1-5 with strong preference for an exposed Asp residue at the N-terminus of the peptide, has undergone advanced clinical testing for treatment of AD.

Methods

To gain further insight into the epitope conformation, we interrogated structural details of amino-terminal epitopes in amyloid-β using x-ray crystallography of 3D6Fab:amyloid-β complexes. Humanization o

SUBMITTER: Feinberg H 

PROVIDER: S-EPMC4095729 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature