Systematic Evaluation of Protein-Small Molecule Hybrids on the Yeast Surface.

ABSTRACT: Protein-small molecule hybrids are structures that have the potential to combine the inhibitory properties of small molecules and the specificities of binding proteins. However, achieving such synergies is a substantial engineering challenge with fundamental principles yet to be elucidated. Recent work has demonstrated the power of the yeast display-based discovery of hybrids using a combination of fibronectin-binding domains and thiol-mediated conjugations to introduce small-molecule warheads. Here, we systematically study the effects of expanding the chemical diversity of these hybrids on the yeast surface by investigating a combinatorial set of fibronectins, noncanonical amino acid (ncAA) substitutions, and small-molecule pharmacophores. Our results show that previously discovered thiol

SUBMITTER: Huang M 

PROVIDER: S-EPMC11146673 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature