A side-by-side biophysical comparison of five single-domain antibody scaffolds used for synthetic display libraries - PubMed
a day ago
- #biophysical comparison
- #synthetic libraries
- #single-domain antibodies
- Systematic comparison of five single-domain antibody (sdAb) scaffolds used in synthetic display libraries using sequence analysis, biophysical assays, and AlphaFold-based structure prediction.
- Evaluated key parameters include humanness, expression yield, hydrophobicity, monomericity, stability, and display efficiency of sdAb scaffolds.
- Camelid sdAbs showed superior biophysical traits but the lowest humanness, while human or humanized VH-based sdAbs had high human sequence homology but biophysical limitations.
- Mutations for improving stability or humanization were observed to compromise other biophysical properties in the studied sdAb scaffolds.
- Findings underscore the complexity of multi-parameter optimization in sdAb development, highlighting the value of synthetic display libraries for therapeutic antibody discovery.