Can I read Mutational Analysis of Domain Antibodies Reveals Aggregation Hotspots Within and Near the Complementarity Determining Regions on EtoBox?

Mutational Analysis of Domain Antibodies Reveals Aggregation Hotspots Within and Near the Complementarity Determining Regions by Joseph M. Perchiacca; Moumita Bhattacharya; Peter M. Tessier is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Mutational Analysis of Domain Antibodies Reveals Aggregation Hotspots Within and Near the Complementarity Determining Regions about?

## Abstract High‐affinity antibodies are critical for numerous diagnostic and therapeutic applications, yet their utility is limited by their variable propensity to aggregate either at low concentrations for antibody fragments or high concentrations for full‐length antibodies. Therefore, determining the sequence and structural features that differentiate aggregation‐resistant antibodies from aggregation‐prone ones is critical to improving their activity. We have investigated the molecular origins of antibody aggregation for human V~H~ domain antibodies that differ only in the sequence of the loops containing their complementarity determining regions (CDRs), yet such antibodies possess dramatically different aggregation propensities in a manner not correlated with their conformational stabilities. We find the propensity of these antibodies to aggregate after being transiently unfolded is not a distributed property of the CDR loops, but can be localized to aggregation hotspots within and near the first CDR (CDR1). Moreover, we have identified a triad of charged mutations within CDR1 and a single charged mutation adjacent to CDR1 that endow the poorly soluble variant with the desirabl

Who reads Mutational Analysis of Domain Antibodies Reveals Aggregation Hotspots Within and Near the Complementarity Determining Regions?

Author

Joseph M. Perchiacca; Moumita Bhattacharya; Peter M. Tessier

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); Wiley-Liss Inc; Wiley (ISSN 0887-3585)

Published

2011

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)