Engineering of three-finger fold toxins creates ligands with original pharmacological profiles for muscarinic and adrenergic receptors.

ABSTRACT: Protein engineering approaches are often a combination of rational design and directed evolution using display technologies. Here, we test "loop grafting," a rational design method, on three-finger fold proteins. These small reticulated proteins have exceptional affinity and specificity for their diverse molecular targets, display protease-resistance, and are highly stable and poorly immunogenic. The wealth of structural knowledge makes them good candidates for protein engineering of new functionality. Our goal is to enhance the efficacy of these mini-proteins by modifying their pharmacological properties in order to extend their use in imaging, diagnostics and therapeutic applications. Using the interaction of three-finger fold toxins with muscarinic and adrenergic receptors as a model, c

SUBMITTER: Fruchart-Gaillard C 

PROVIDER: S-EPMC3375269 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature