Rational antibody design for undruggable targets using kinetically controlled biomolecular probes.

ABSTRACT: Several important drug targets, e.g., ion channels and G protein-coupled receptors, are extremely difficult to approach with current antibody technologies. To address these targets classes, we explored kinetically controlled proteases as structural dynamics-sensitive druggability probes in native-state and disease-relevant proteins. By using low-Reynolds number flows, such that a single or a few protease incisions are made, we could identify antibody binding sites (epitopes) that were translated into short-sequence antigens for antibody production. We obtained molecular-level information of the epitope-paratope region and could produce high-affinity antibodies with programmed pharmacological function against difficult-to-drug targets. We demonstrate the first stimulus-selective monoclonal

SUBMITTER: Trkulja CL 

PROVIDER: S-EPMC8051879 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature