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Structure-based design used as tool for engineering deimmunized biotherapeutics

investigators engineer drug candidates for improved compatibility with immune system

Peptide Backbone
The P99 beta lactamase peptide backbone is shown in complex with a beta lactam substrate (PDB file 4KEN), which is rendered as a stick figure with carbon in cyan, nitrogen in dark blue, oxygen in red, and sulfur in yellow. Shown as thick green tubes are overlapping immunogenic epitopes targeted for deletion by introduction of structurally optimized deimmunizing mutations, whose positions are shown as blue spheres. Structure based deimmunization enabled targeting of high risk immunogenic subsequences that were located both distal and proximal to the enzyme’s active site.
Credit: NCCC


Source

Protein deimmunization via structure-based design enables efficient epitope deletion at high mutational loads. DOI: 10.1002/bit.25554

Karl Griswold, PhD is Associate Professor of Engineering at the Thayer School of Engineering at Dartmouth. His work in cancer is facilitated by Dartmouth’s . Christopher Bailey-Kellogg, PhD is Professor of Computer Science at . This work was funded by National Institutes of Health grant RO1-GM-098977, a Luce Foundation Fellowship, and National Science Foundation grant CNS-1205521.

The Geisel School of Medicine at Dartmouth