Journal article

Crystallization and preliminary X-ray diffraction analysis of the Fab portion of the Alzheimer's disease immunotherapy candidate bapineuzumab complexed with amyloid-beta

Gabriela AN Crespi, David B Ascher, Michael W Parker, Luke A Miles

Acta Crystallographica Section F: Structural Biology Communications | INT UNION CRYSTALLOGRAPHY | Published : 2014

Abstract

Bapineuzumab (AAB-001) and its derivative (AAB-003) are humanized versions of the anti-Aβ murine antibody 3D6 and are immunotherapy candidates in Alzheimer's disease. The common Fab fragment of these immunotherapies has been expressed, purified and crystallized in complex with β-amyloid peptides (residues 1-8 and 1-28). Diffraction data at high resolution were acquired from crystals of Fab-Aβ8 (2.0 Å) and Fab-Aβ28 (2.2 Å) complexes at the Australian Synchrotron. Both crystal forms belonged to the primitive orthorhombic space group P21221.

Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)


Funding Acknowledgements

We would like to thank Aidan Williams at Emmanuel College for his contribution to validating Fab binding to A beta. This research was partly undertaken on the MX1 and MX2 beamlines at the Australian Synchrotron, Victoria, Australia. This work was supported by funding from a National Health and Medical Research Council of Australia (NHMRC) Project Grant (APP1021935) and grants from the JO & JR Wicking Trust, The Mason Foundation and The Bethlehem Griffith Research Foundation to MWP and LAM. The Australian Cancer Research Foundation provided substantial funding support for equipment critical for this work. Infrastructure support from the NHMRC Independent Research Institutes Infrastructure Support Scheme and the Victorian State Government Operational Infrastructure Support Program are gratefully acknowledged. DBA was supported by a Victoria Fellowship from the Victorian Government and the Leslie (Les) J. Fleming Churchill Fellowship from The Winston Churchill Memorial Trust. MWP is an NHMRC Research Fellow.