{"doi":"10.3389/bjbs.2025.15526","title":"7-Methylguanine With a Cyclopentane Backbone: A Bright Combination for a FIT-PNA RNA Sensor","abstract":"FIT-PNAs (forced intercalation-Peptide Nucleic Acids) are promising RNA sensors due to the enhanced fluorescence gained by such molecules upon RNA hybridization. In this report we describe a chemical approach that leads to unprecedented brightness for a FIT-PNA where the neighbouring Guanine base (G) to the fluorophore (a.k.a. surrogate base) is chemically modified with a cyclopentane (cp) backbone and is N-methylated, leading to a positively charged (G + ) base. A series of G modified bases (G + , cpG, and cpG + ) were introduced as the neighbouring base to BisQ (surrogate base) in 15-mer FIT-PNAs designed to sense the oncogenic long-noncoding RNA, colon cancer associated transcript 1 (lncRNA CCTA-1). Using synthetic RNA, the combination denoted as cpG + led to a two-fold increase in brightness (BR = 16.9) compared to the unmodified G base (BR = 8.4). Introducing a G mismatch in RNA sequence that is opposite to the G base (G, G + , cpG, or cpG + ) in the FIT-PNA, led to an increase in fluorescence that was not observed for synthetic DNA. Molecular simulations confirmed these observations and further correlated fluorescence data for FIT-PNAs with synthetic DNA and RNA with/out mismatches. Importantly, in ovarian cancer cells overexpressing CCAT1, only the cpG + modified FIT-PNA produced a bright fluorescent signal, confirmed by FACS and confocal microscopy. Our results demonstrate that strategic chemical modifications of the neighboring G base in FIT-PNA significantly enhance their brightness and specificity for RNA detection in biological systems.","journal":"British Journal of Biomedical Science","year":2025,"id":535476,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"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":1419555,"name":"Pinaki Chanda","orcid":null,"position":1,"is_corresponding":false},{"id":1419085,"name":"Sheethal Thomas Mannully","orcid":"0000-0002-7415-8797","position":2,"is_corresponding":false},{"id":487248,"name":"Hongchao Zheng","orcid":"0000-0003-2205-175X","position":3,"is_corresponding":false},{"id":383718,"name":"Daniel H. Appella","orcid":"0000-0001-7195-7764","position":4,"is_corresponding":false},{"id":1241682,"name":"Eylon Yavin","orcid":"0000-0002-3527-3215","position":5,"is_corresponding":false},{"id":1419554,"name":"Salam Maree","orcid":null,"position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:51:56.297114Z","pmid":"41356095","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":[]}