Structure-based design of macrocyclic peptides to generate functional antibodies against G protein-coupled receptors.

ABSTRACT: G protein-coupled receptors (GPCRs) are critical to a variety of pathophysiological processes, making them attractive targets for the development of drugs or relevant diagnostic tools. Although GPCRs have been successfully targeted with small molecules, the production of reliable anti-GPCR antibodies remains a major challenge. To address this issue, we develop a strategy using macrocyclic peptides designed to mimic the three-dimensional structure of GPCR extracellular loops as immunogens and use the chicken, which is genetically distant from mammals, as an immunization host to produce antigen-specific antibodies. The high-affinity neurotensin receptor type 1 (NTS1), overexpressed in many types of human cancer and associated with poor prognosis, is used as a target. Rational design of macro

SUBMITTER: Nepveu-Traversy ME 

PROVIDER: S-EPMC12715230 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature