{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:15:49Z","timestamp":1788290149647,"version":"build-2803163510"},"reference-count":43,"publisher":"American Chemical Society (ACS)","issue":"34","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100024236","name":"Indian Association for the Cultivation of Science","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100024236","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The structural interconversion between the G-quadruplex (G4) and duplex DNA is central to many biological processes, yet the factors governing this transition remain incompletely understood. Here, we systematically examine the roles of guanine (G)-tract length and loop architecture in modulating the kinetics of the G4-to-duplex transition using circular dichroism (CD), NMR spectroscopy, gel electrophoresis and time-dependent FRET measurements. Our results show that increasing the number of guanines in the G-tract significantly enhances the G4 stability and reduces the propensity for duplex formation. Sequences with shorter G-tracts undergo rapid conversion to duplex upon the addition of complementary strands, whereas those with longer G-tracts exhibit slower kinetics or remain predominantly in the G4 state. Binding studies reveal that the affinity of the complementary strand decreases markedly with an increasing G-tract length, establishing an inverse correlation between G4 stability and duplex formation. Kinetic analyses further indicate the presence of multiple G4 conformational populations that interconvert at distinct rates, reflecting the structural heterogeneity in the G4 ensemble. In contrast, variations in loop length exert a relatively modest and nonmonotonic effect on binding affinity but significantly influence the kinetics of the transition. Increasing the loop length reduces structural inhomogeneity and enhances the contribution of the fast-converting population. Overall, these findings demonstrate that the G-tract length is the dominant factor controlling G4 stability and duplex conversion, whereas the loop length and composition fine-tune the kinetic pathways by modulating the underlying conformational landscape. This study provides molecular-level insight into the role of the G-tract and loop nucleobases of the G4 in the structural transition from the G4 to the duplex.<\/jats:p>","DOI":"10.1021\/acs.jpcb.6c02773","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T21:01:26Z","timestamp":1786741286000},"page":"8590-8598","source":"Crossref","is-referenced-by-count":0,"title":["G-Quadruplex\nto Duplex Conversion: The Role\nof Guanine Quartet versus Loop"],"prefix":"10.1021","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6963-4325","authenticated-orcid":true,"given":"Asim","family":"Bisoi","sequence":"first","affiliation":[{"name":"Indian Association for the Cultivation of Science , , Jadavpur , ,","place":["Kolkata, India, 700032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0842-8140","authenticated-orcid":true,"given":"Trideep","family":"Majumdar","sequence":"additional","affiliation":[{"name":"Indian Association for the Cultivation of Science , , Jadavpur , ,","place":["Kolkata, India, 700032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9357-9039","authenticated-orcid":true,"given":"Prashant Chandra","family":"Singh","sequence":"additional","affiliation":[{"name":"Indian Association for the Cultivation of Science , , Jadavpur , ,","place":["Kolkata, India, 700032"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"2026090114352124100_cit1","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.trechm.2019.07.002","article-title":"The Structure and Function of DNA\nG-Quadruplexes","volume":"2","author":"Spiegel","year":"2020","journal-title":"Trends Chem."},{"key":"2026090114352124100_cit2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142700.nc1705s50","article-title":"Sequence, stability,\nand structure of G-quadruplexes and their interactions\nwith drugs","volume":"50","author":"Chen","year":"2012","journal-title":"Curr. Protoc. Nucleic Acid Chem."},{"key":"2026090114352124100_cit3","doi-asserted-by":"publisher","first-page":"5402","DOI":"10.1093\/nar\/gkl655","article-title":"Quadruplex\nDNA: sequence, topology and structure","volume":"34","author":"Burge","year":"2006","journal-title":"Nucleic\nAcids Res."},{"key":"2026090114352124100_cit4","doi-asserted-by":"publisher","first-page":"11736","DOI":"10.1021\/bi034168j","article-title":"Structural Competition\nInvolving G-Quadruplex DNA and Its Complement","volume":"42","author":"Li","year":"2003","journal-title":"Biochemistry"},{"key":"2026090114352124100_cit5","doi-asserted-by":"publisher","first-page":"4433","DOI":"10.1093\/nar\/gkn402","article-title":"Effect of\nloop length variation on quadruplex-Watson Crick duplex competition","volume":"36","author":"Kumar","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2026090114352124100_cit6","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.biochi.2015.09.031","article-title":"Kinetics of quadruplex to duplex\nconversion","volume":"118","author":"Mendoza","year":"2015","journal-title":"Biochimie"},{"key":"2026090114352124100_cit7","doi-asserted-by":"publisher","first-page":"3628","DOI":"10.1111\/j.1742-4658.2009.07082.x","article-title":"Effect of\nflanking bases on quadruplex\nstability and Watson\u2013Crick duplex competition","volume":"276","author":"Arora","year":"2009","journal-title":"FEBS. J."},{"key":"2026090114352124100_cit8","doi-asserted-by":"publisher","first-page":"7484","DOI":"10.1021\/ja070497d","article-title":"Single-Molecule\nConformational Analysis of G-Quadruplex Formation in the Promoter\nDNA Duplex of the Proto-Oncogene C-Kit","volume":"129","author":"Shirude","year":"2007","journal-title":"J. Am.\nChem. Soc."},{"key":"2026090114352124100_cit9","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1002\/bip.360350613","article-title":"Duplex to quadruplex\nequilibrium of the self-complementary\noligonucleotide d(GGGGCCCC)","volume":"35","author":"Deng","year":"1995","journal-title":"Biopolymers"},{"key":"2026090114352124100_cit10","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/s41580-020-0236-x","article-title":"The regulation and functions of DNA\nand RNA G-quadruplexes","volume":"21","author":"Varshney","year":"2020","journal-title":"Nat. Rev. Mol. Cell\nBiol."},{"key":"2026090114352124100_cit11","doi-asserted-by":"publisher","first-page":"8627","DOI":"10.1093\/nar\/gkv862","article-title":"G-quadruplexes and their regulatory roles in biology","volume":"43","author":"Rhodes","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2026090114352124100_cit12","doi-asserted-by":"publisher","first-page":"11364","DOI":"10.1021\/jacs.4c00960","article-title":"DNA Damage Accelerates\nG-Quadruplex Folding in a Duplex-G-Quadruplex-Duplex Context","volume":"146","author":"Fleming","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"2026090114352124100_cit13","doi-asserted-by":"publisher","first-page":"6723","DOI":"10.1093\/nar\/gki961","article-title":"The effect of osmolytes and small molecule on Quadruplex\u2013WC\nduplex equilibrium: a fluorescence resonance energy transfer study","volume":"33","author":"Kumar","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2026090114352124100_cit14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2020.106473","article-title":"Duplex-tetraplex equilibria in guanine-\nand cytosine-rich DNA","volume":"267","author":"Chalikian","year":"2020","journal-title":"Biophys. Chem."},{"key":"2026090114352124100_cit15","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S0014-5793(02)03118-6","article-title":"Characterization and thermodynamic\nproperties of quadruplex\/duplex competition","volume":"526","author":"Li","year":"2002","journal-title":"FEBS Lett."},{"key":"2026090114352124100_cit16","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1007\/s10973-015-4588-y","article-title":"How are thermodynamically stable\nG-quadruplex\u2013duplex hybrids?","volume":"121","author":"Fotticchia","year":"2015","journal-title":"J. Therm.\nAnal. Calorim."},{"key":"2026090114352124100_cit17","doi-asserted-by":"publisher","first-page":"5482","DOI":"10.1093\/nar\/gkn517","article-title":"Stability\nand kinetics\nof G-quadruplex structures","volume":"36","author":"Lane","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2026090114352124100_cit18","doi-asserted-by":"publisher","first-page":"7848","DOI":"10.1021\/bi00191a012","article-title":"Structural Polymorphism of Telomere\nDNA: Interquadruplex and Duplex-Quadruplex Conversions Probed by Raman\nSpectroscopy","volume":"33","author":"Miura","year":"1994","journal-title":"Biochemistry"},{"key":"2026090114352124100_cit19","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1021\/acs.biochem.5c00486","article-title":"Three-State\nUnfolding of Telomeric G-Quadruplexes through Conformational Switching\nin Crowded Cell-like Conditions","volume":"65","author":"Majumdar","year":"2026","journal-title":"Biochemistry"},{"key":"2026090114352124100_cit20","doi-asserted-by":"publisher","first-page":"13297","DOI":"10.3390\/molecules181113297","article-title":"Effect of Pressure\non Thermal Stability of G-Quadruplex\nDNA and Double-Stranded DNA Structures","volume":"18","author":"Takahashi","year":"2013","journal-title":"Molecules"},{"key":"2026090114352124100_cit21","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1002\/bip.20609","article-title":"Electrostatics dominate\nquadruplex stability","volume":"85","author":"Smirnov","year":"2007","journal-title":"Biopolymers"},{"key":"2026090114352124100_cit22","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1093\/nar\/gkp898","article-title":"Molecular crowding\ncreates an essential environment for the formation of stable G-quadruplexes\nin long double-stranded DNA","volume":"38","author":"Zheng","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2026090114352124100_cit23","doi-asserted-by":"publisher","first-page":"4510","DOI":"10.1021\/acs.jpclett.3c00214","article-title":"Chemical Interaction\nRegulates the Folding and Topology\nof the G-Quadruplex Exclusively Induced by a Crowder","volume":"14","author":"Bisoi","year":"2023","journal-title":"J. Phys. Chem. Lett."},{"key":"2026090114352124100_cit24","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2016.00038","article-title":"Metal Cations in G-Quadruplex\nFolding\nand Stability","volume":"4","author":"Bhattacharyya","year":"2016","journal-title":"Front. Chem."},{"key":"2026090114352124100_cit25","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.ymeth.2007.05.004","article-title":"Quadruplex melting","volume":"43","author":"Rachwal","year":"2007","journal-title":"Methods"},{"key":"2026090114352124100_cit26","doi-asserted-by":"publisher","first-page":"17.1.1","DOI":"10.1002\/0471142700.nc1701s37","article-title":"UV Melting of G-Quadruplexes","volume":"37","author":"Mergny","year":"2009","journal-title":"Curr. Protoc. Nucleic Acid Chem."},{"key":"2026090114352124100_cit27","doi-asserted-by":"publisher","DOI":"10.1002\/0471142700.nc1704s45","article-title":"Analysis of multidimensional G-quadruplex\nmelting curves","volume":"17","author":"Gray","year":"2011","journal-title":"Curr. Protoc. Nucleic Acid Chem."},{"key":"2026090114352124100_cit28","doi-asserted-by":"publisher","first-page":"4618","DOI":"10.1093\/nar\/gkf597","article-title":"Human telomeric\nDNA: G-quadruplex, i-motif and Watson\u2013Crick\ndouble helix","volume":"30","author":"Phan","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2026090114352124100_cit29","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1093\/nar\/gkad1073","article-title":"A sodium\/potassium\nswitch for G4-prone\nG\/C-rich sequences","volume":"52","author":"Luo","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"2026090114352124100_cit30","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1016\/j.biochi.2009.05.014","article-title":"Human telomeric\nG-quadruplex formed from duplex under near physiological conditions:\nSpectroscopic evidence and kinetics","volume":"91","author":"Zhou","year":"2009","journal-title":"Biochimie"},{"key":"2026090114352124100_cit31","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1007\/s00249-025-01772-w","article-title":"Quadruplexes with a grain of salt:\ninfluence of cation\ntype and concentration on DNA G4 stability","volume":"54","author":"Cucchiarini","year":"2025","journal-title":"Eur. Biophys. J."},{"key":"2026090114352124100_cit32","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1093\/nass\/nrn080","article-title":"Role of Molecular Crowding in perturbing\nQuadruplex-Watson Crick\nDuplex Equilibrium","volume":"52","author":"Kumar","year":"2008","journal-title":"Nucleic Acids Symp. Ser."},{"key":"2026090114352124100_cit33","doi-asserted-by":"publisher","first-page":"9264","DOI":"10.1093\/nar\/gky757","article-title":"Loop permutation affects\nthe topology\nand stability of G-quadruplexes","volume":"46","author":"Cheng","year":"2018","journal-title":"Nucleic Acids\nRes."},{"key":"2026090114352124100_cit34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.131050","article-title":"Loop nucleobases-dependent\nfolding\nof G-quadruplex in normal and cancer cell-mimicking KCl microenvironments","volume":"265","author":"Bisoi","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"2026090114352124100_cit35","doi-asserted-by":"publisher","first-page":"4159","DOI":"10.1021\/acs.jpcb.5c00526","article-title":"Nucleobase Level\nInformation into the Folding of G-Quadruplex by Anti-inflammatory\nDrugs in the Absence of Salt","volume":"129","author":"Bisoi","year":"2025","journal-title":"J. Phys. Chem.\nB"},{"key":"2026090114352124100_cit36","doi-asserted-by":"publisher","first-page":"3036","DOI":"10.1021\/bi062118j","article-title":"Effect of G-Tract Length on the Topology\nand Stability of Intramolecular DNA Quadruplexes","volume":"46","author":"Rachwal","year":"2007","journal-title":"Biochemistry"},{"key":"2026090114352124100_cit37","doi-asserted-by":"publisher","DOI":"10.1116\/6.0004389","article-title":"Insight into the\nrole of the chemical nature and length\nof the loop nucleobases in the folding of G-quadruplex by the antimalarial\ndrugs at the DNA interface","volume":"20","author":"Bisoi","year":"2025","journal-title":"Biointerphases"},{"key":"2026090114352124100_cit38","doi-asserted-by":"publisher","first-page":"4214","DOI":"10.1093\/nar\/gkm316","article-title":"Intramolecular\nDNA quadruplexes with different arrangements of short and long loops","volume":"35","author":"Rachwal","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2026090114352124100_cit39","doi-asserted-by":"publisher","first-page":"6648","DOI":"10.1021\/acs.jpcb.3c03042","article-title":"Antimalarial Drugs Induce the Selective\nFolding of Human Telomeric G-Quadruplex in a Cancer-Mimicking Microenvironment","volume":"127","author":"Sarkar","year":"2023","journal-title":"J. Phys. Chem. B"},{"key":"2026090114352124100_cit40","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.ymeth.2012.03.011","article-title":"Circular dichroism and guanine quadruplexes","volume":"57","author":"Vorli\u0301c\u030ckova\u0301","year":"2012","journal-title":"Methods"},{"key":"2026090114352124100_cit41","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1093\/nar\/gkp026","article-title":"Circular dichroism\nand conformational polymorphism of DNA","volume":"37","author":"Kypr","year":"2009","journal-title":"Nucleic\nAcids Res."},{"key":"2026090114352124100_cit42","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1093\/nar\/30.7.1500","article-title":"NMR structure of a parallel-stranded\nDNA duplex at atomic resolution","volume":"30","author":"Parvathy","year":"2002","journal-title":"Nucleic Acids\nRes."},{"key":"2026090114352124100_cit43","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/978-1-4939-9666-7_9","article-title":"NMR Studies of G-Quadruplex Structures\nand G-Quadruplex-Interactive Compounds","volume":"2035","author":"Lin","year":"2019","journal-title":"Methods\nMol. Biol."}],"container-title":["The Journal of Physical\nChemistry B"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jpcb.6c02773","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article-pdf\/130\/34\/8590\/66568886\/acs.jpcb.6c02773.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article-pdf\/130\/34\/8590\/66568886\/acs.jpcb.6c02773.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T18:35:28Z","timestamp":1788287728000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article\/130\/34\/8590\/5256828\/G-Quadruplex-to-Duplex-Conversion-The-Role-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":43,"journal-issue":{"issue":"34","published-online":{"date-parts":[[2026,8,14]]},"published-print":{"date-parts":[[2026,8,27]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jpcb.6c02773","relation":{},"ISSN":["1520-6106","1520-5207"],"issn-type":[{"value":"1520-6106","type":"print"},{"value":"1520-5207","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}