High-Throughput Identification and Characterization of LptDE-Binding Bicycle Peptides Using Phage Display and Cryo-EM.

ABSTRACT: The lipopolysaccharide (LPS) transport (Lpt) system in Gram-negative bacteria maintains the integrity of the asymmetric bacterial outer membrane (OM). LPS biogenesis systems are essential in most Gram-negative bacteria, with LptDE responsible for the delivery of LPS to the outer leaflet of the OM. As an externally accessible, essential protein, LptDE offers a promising target for inhibitor development without the need for cellular penetration. However, there are no direct inhibitors of E. coli LptDE, and drug discovery is made challenging since it is a membrane target without a conventional active site. Here, the bicycle phage display platform was used in combination with cryogenic-electron microscopy (cryo-EM) and surface plasmon resonance to identify and map bicyclic peptide binde

SUBMITTER: Allyjaun S 

PROVIDER: S-EPMC12557396 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature