{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Allyjaun S"],"funding":["Innovate UK","Barbour Foundation","Medical Research Council"],"pagination":["21144-21155"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12557396"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["68(20)"],"pubmed_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 <i>E. coli</i> 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"],"journal":["Journal of medicinal chemistry"],"pubmed_title":["High-Throughput Identification and Characterization of LptDE-Binding Bicycle Peptides Using Phage Display and Cryo-EM."],"pmcid":["PMC12557396"],"funding_grant_id":["328081","U-016275","10086683","MR/X50290X/1"],"pubmed_authors":["Cooper L","Paris G","Hubbard J","van den Berg B","Lewis N","Dunbar E","Holding F","Arruda Bezerra G","St Denis MA","Newman H","Bournakas N","Chirgadze DY","Brown P","Skynner MJ","Hardwick SW","Dawson MJ","Beswick P","Pellegrino S","Newell S","Rowland CE","Allyjaun S"],"additional_accession":[]},"is_claimable":false,"name":"High-Throughput Identification and Characterization of LptDE-Binding Bicycle Peptides Using Phage Display and Cryo-EM.","description":"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 <i>E. coli</i> 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","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-05T06:41:13.436Z","creation":"2026-06-05T03:06:43.779Z"},"accession":"S-EPMC12557396","cross_references":{"pubmed":["41048016"],"doi":["10.1021/acs.jmedchem.5c00307"]}}