AI-Driven De Novo Design of Ultra Long-Acting GLP-1 Receptor Agonists.

ABSTRACT: Peptide drugs have revolutionized modern therapeutics, offering novel treatment avenues for various diseases. Nevertheless, low design efficacy, time consumption, and high cost still hinder peptide drug design and discovery. Here, an efficient approach that integrates deep learning-based protein design with functional screening is presented, enabling the rapid design of biotechnologically important peptides with improved stability and efficacy. 10,000 de novo glucagon-like peptide-1 receptor agonists (GLP-1RAs) are designed, 60 of these satisfied the stability, efficacy, and diversity criteria in the virtual functional screening. In vitro validations reveal a 52% success rate, and in vivo experiments demonstrate that two lead GLP-1RAs (D13 and D41) exhibit extended half-lives, approximatel

SUBMITTER: Wei T 

PROVIDER: S-EPMC12561408 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature