{"doi":"10.1021/acschembio.4c00720","title":"Silyl-Lipid Functionalized <i>N</i>-Acyl Homoserine Lactones as Modulators of Bacterial Cell–Cell Communication","abstract":"High Resolution Image Download MS PowerPoint Slide We report silyl-lipid derivatives of N -acyl l -homoserine lactones (AHLs) that have nanomolar activities in LuxR-type quorum sensing receptors in Gram-negative bacterial pathogens. A collection of silyl-lipid AHLs were designed and synthesized to represent three general structural classes based on native AHL signals and synthetic LuxR-type receptor modulators. The synthetic routes feature straightforward hydrosilylation and aryl silylation reactions to access silyl-lipid groups that are not readily accessible in analogous all-carbon chemistry. Of the 17 compounds evaluated, eight silyl-lipid AHLs were identified with either nanomolar agonistic or submicromolar antagonistic activities in the LasR receptor from the common pathogen Pseudomonas aeruginosa using E. coli reporter gene assays. Several silyl-lipid AHL agonists retained high activities in LasR in a native P. aeruginosa reporter system and also were active in another related LuxR-type receptor, EsaR from Pantoea stewartii . Light scattering and computational experiments indicate that the silyl-lipid group can alter the aggregation capabilities and lipophilicities of AHLs relative to native all-carbon tails, engendering larger aggregate formation in water and higher lipophilicities on average. These properties, along with their strong activity profiles in LuxR-type receptors, suggest silyl-lipid AHLs could provide value as chemical probes to study the mechanisms of quorum sensing in Gram-negative bacteria and the roles of signal lipophilicity in this chemical communication process.","journal":"ACS Chemical Biology","year":2025,"id":562061,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":915403,"name":"Emma E. Santa","orcid":"0000-0003-3315-4690","position":1,"is_corresponding":false},{"id":1334556,"name":"Irene M. Stoutland","orcid":null,"position":2,"is_corresponding":false},{"id":1464505,"name":"Kelsey M. Mesa","orcid":null,"position":3,"is_corresponding":false},{"id":1464506,"name":"Cole C. Dickson","orcid":null,"position":4,"is_corresponding":false},{"id":721598,"name":"Helen E. Blackwell","orcid":"0000-0003-4261-8194","position":5,"is_corresponding":false},{"id":1336534,"name":"Annaliese K. Franz","orcid":"0000-0002-4841-2448","position":6,"is_corresponding":false},{"id":1464504,"name":"Linnea S. Dolph","orcid":null,"position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:56:01.883848Z","pmid":"39945376","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}