{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:05:58Z","timestamp":1787317558111,"version":"build-2736575974"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontierspartnerships.org"],"crossmark-restriction":true},"short-container-title":["Br. J. Biomed. Sci."],"abstract":"<jats:p>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    ) base. A series of G modified bases (G\n                    <jats:sup>+<\/jats:sup>\n                    , cpG, and cpG\n                    <jats:sup>+<\/jats:sup>\n                    ) 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\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    , cpG, or cpG\n                    <jats:sup>+<\/jats:sup>\n                    ) 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\n                    <jats:sup>+<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.3389\/bjbs.2025.15526","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T06:10:24Z","timestamp":1763705424000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["7-Methylguanine With a Cyclopentane Backbone: A Bright Combination for a FIT-PNA RNA Sensor"],"prefix":"10.3389","volume":"82","author":[{"given":"Salam","family":"Maree","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinaki","family":"Chanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheethal Thomas","family":"Mannully","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchao","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Appella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eylon","family":"Yavin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1016\/0006-2952(94)90171-6","article-title":"Stability of Peptide Nucleic-Acids in Human Serum and Cellular-Extracts","volume":"48","author":"Demidov","year":"1994","journal-title":"Biochem Pharm"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2405","DOI":"10.1039\/c5cc07502e","article-title":"Single Point Mutation Detection 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