Single-chain dimers from de novo immunoglobulins as robust scaffolds for multiple binding loops.

ABSTRACT: Antibody derivatives have sought to recapitulate the antigen binding properties of antibodies, but with improved biophysical attributes convenient for therapeutic, diagnostic and research applications. However, their success has been limited by the naturally occurring structure of the immunoglobulin dimer displaying hypervariable binding loops, which is hard to modify by traditional engineering approaches. Here, we devise geometrical principles for de novo designing single-chain immunoglobulin dimers, as a tunable two-domain architecture that optimizes biophysical properties through more favorable dimer interfaces. Guided by these principles, we computationally designed protein scaffolds that were hyperstable, structurally accurate and robust for accommodating multiple functional loops, bo

SUBMITTER: Roel-Touris J 

PROVIDER: S-EPMC10517939 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature