{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T16:16:23Z","timestamp":1789488983556,"version":"build-2803163510"},"reference-count":45,"publisher":"American Chemical Society (ACS)","issue":"26","license":[{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100012323","name":"CSIR - Indian Institute of Chemical Biology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012323","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SERB, India","award":["CRG\/2019\/001788"],"award-info":[{"award-number":["CRG\/2019\/001788"]}]},{"name":"SERB, India","award":["SB\/SO\/BB-0025\/2014"],"award-info":[{"award-number":["SB\/SO\/BB-0025\/2014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pathogenesis of Alzheimer\u2019s disease (AD), the most common type of dementia, involves misfolding and aggregation of the extracellular amyloid-\u03b2 (A\u03b2) protein where the intermediate oligomers, formed during the aggregation progression cascade, are considered the prime toxic species. Here, we identify an active peptide fragment from a medicinal plant-derived (Aristolochia indica) fibrinolytic enzyme having anti-amyloidogenic effects against A\u03b2 fibrillation and toxicity. Liquid chromatography with tandem mass spectrometry (LC-MS\/MS), followed by computational analysis of the peptide pool generated by proteolytic digestion of the enzyme, identifies two peptide sequences with predictive high-propensity binding to A\u03b242. Microscopic visualizations in conjunction with biochemical and biophysical assessments suggest that the synthetic version of one of the peptides (termed here Pactive, GFLLHQK) arrests A\u03b2 molecules in off-pathway oligomers that can no longer participate in the cytotoxic fibrillation pathway. In contrast, the other peptide (termed P1) aggravates the fibrillation process. Further investigations confirm the strong binding affinity of Pactive with both A\u03b242 monomers and toxic oligomers by biolayer interferometric assays. We have also shown that, mechanistically, Pactive binding induces conformational alterations in the A\u03b2 molecule along with modification of A\u03b2 hydrophobicity, one of the key players in aggregation. Importantly, the biostability of Pactive in human blood serum and its nontoxic nature make it a promising therapeutic candidate against Alzheimer\u2019s, for which no disease-modifying treatments are available to date.<\/jats:p>","DOI":"10.1021\/acsomega.0c01730","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T08:42:06Z","timestamp":1593074526000},"page":"16128-16138","source":"Crossref","is-referenced-by-count":5,"title":["Heptameric Peptide Interferes with Amyloid-\u03b2\nAggregation by Structural Reorganization of the Toxic Oligomers"],"prefix":"10.1021","volume":"5","author":[{"given":"Rajanya","family":"Bhattacharyya","sequence":"first","affiliation":[{"name":"CSIR-Indian Institute of Chemical Biology , , 4, Raja S.C. Mullick Road , ,","place":["Kolkata, India, 700032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayan","family":"Bhattacharjee","sequence":"additional","affiliation":[{"name":"CSIR-Indian Institute of Chemical Biology , , 4, Raja S.C. Mullick Road , ,","place":["Kolkata, India, 700032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bani K.","family":"Pathak","sequence":"additional","affiliation":[{"name":"CSIR-Indian Institute of Chemical Biology , , 4, Raja S.C. Mullick Road , ,","place":["Kolkata, India, 700032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3614-6047","authenticated-orcid":true,"given":"Jayati","family":"Sengupta","sequence":"additional","affiliation":[{"name":"CSIR-Indian Institute of Chemical Biology , , 4, Raja S.C. Mullick Road , ,","place":["Kolkata, India, 700032"]},{"name":"Academy of Scientific and Innovative Research (AcSIR) , ,","place":["Ghaziabad, India, 201002"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"key":"2026091511095391000_cit1a","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1002\/ca.980080612","article-title":"An English translation of Alzheimer\u2019s\n1907 paper,\n\u2033Uber eine eigenartige Erkankung der Hirnrinde\u2033","volume":"8","author":"Alzheimer","year":"1995","journal-title":"Clin. Anat."},{"key":"2026091511095391000_cit1b","doi-asserted-by":"publisher","first-page":"S10","DOI":"10.1038\/nm1066","article-title":"Protein aggregation and neurodegenerative\ndisease","volume":"10","author":"Ross","year":"2004","journal-title":"Nat. Med."},{"key":"2026091511095391000_cit1c","doi-asserted-by":"publisher","first-page":"451","DOI":"10.2119\/2007-00100.Irvine","article-title":"Protein aggregation\nin the brain: the molecular basis for Alzheimer\u2019s and Parkinson\u2019s\ndiseases","volume":"14","author":"Irvine","year":"2008","journal-title":"Mol. Med."},{"key":"2026091511095391000_cit2","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/nchembio.624","article-title":"Amyloid-beta forms\nfibrils by nucleated conformational conversion of oligomers","volume":"7","author":"Lee","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"2026091511095391000_cit3a","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/nature04533","article-title":"A specific amyloid-beta protein assembly in the brain\nimpairs memory","volume":"440","author":"Lesne","year":"2006","journal-title":"Nature"},{"key":"2026091511095391000_cit3b","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1111\/j.1742-4658.2010.07568.x","article-title":"Amyloid oligomers: formation and toxicity of Abeta oligomers","volume":"277","author":"Sakono","year":"2010","journal-title":"FEBS J."},{"key":"2026091511095391000_cit3c","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nn.3028","article-title":"The toxic\nAbeta oligomer and Alzheimer\u2019s disease: an emperor in need\nof clothes","volume":"15","author":"Benilova","year":"2012","journal-title":"Nat. Neurosci."},{"key":"2026091511095391000_cit4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141986","article-title":"An Enzyme from Aristolochia indica Destabilizes Fibrin-beta\nAmyloid Co-Aggregate: Implication in Cerebrovascular Diseases","volume":"10","author":"Bhattacharjee","year":"2015","journal-title":"PLoS One"},{"key":"2026091511095391000_cit5a","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/S1359-6446(04)03104-6","article-title":"Phage display-derived\npeptides as therapeutic alternatives\nto antibodies","volume":"9","author":"Ladner","year":"2004","journal-title":"Drug Discovery Today"},{"key":"2026091511095391000_cit5b","doi-asserted-by":"publisher","first-page":"P352","DOI":"10.1016\/j.jalz.2015.06.235","article-title":"Inhibitors\nof amyloid beta peptide aggregation: Toward new drugs against Alzheimer\u2019s\ndisease","volume":"11","author":"Berthoumieu","year":"2015","journal-title":"Alzheimer\u2019s Dementia"},{"key":"2026091511095391000_cit5c","doi-asserted-by":"publisher","first-page":"4690","DOI":"10.1039\/C6CS00076B","article-title":"Blood-brain\nbarrier shuttle peptides: an emerging paradigm for brain delivery","volume":"45","author":"Oller-Salvia","year":"2016","journal-title":"Chem. 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Pharmacother."},{"key":"2026091511095391000_cit5f","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23020283","article-title":"Peptides as Potential Therapeutics\nfor Alzheimer\u2019s Disease","volume":"23","author":"Ribaric\u030c","year":"2018","journal-title":"Molecules"},{"key":"2026091511095391000_cit5g","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1021\/acschemneuro.6b00175","article-title":"Natural Tripeptide-Based\nInhibitor of Multifaceted Amyloid beta Toxicity","volume":"7","author":"Rajasekhar","year":"2016","journal-title":"ACS Chem. Neurosci."},{"key":"2026091511095391000_cit5h","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s10989-017-9602-8","article-title":"A Peptide Based Pro-drug Disrupts\nAlzheimer\u2019s Amyloid into Non-toxic Species and Reduces A\u03b2\nInduced Toxicity In Vitro","volume":"24","author":"Paul","year":"2017","journal-title":"Int. J. Pept. Res.\nTher."},{"key":"2026091511095391000_cit5i","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00054","article-title":"Structure-Based\nPeptide Inhibitor Design of Amyloid-beta Aggregation","volume":"12","author":"Lu","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"2026091511095391000_cit6","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1006\/abio.1997.2170","article-title":"Zymography: a single-step\nstaining method for quantitation\nof proteolytic activity on substrate gels","volume":"249","author":"Leber","year":"1997","journal-title":"Anal.\nBiochem."},{"key":"2026091511095391000_cit7","doi-asserted-by":"publisher","DOI":"10.1002\/9780470027318.a9038","article-title":"Amyloids and Protein Aggregation\u2500Analytical\nMethods","author":"Li","year":"2009","journal-title":"Encycl. Anal. 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Biochem."},{"key":"2026091511095391000_cit10","doi-asserted-by":"publisher","first-page":"W423","DOI":"10.1093\/nar\/gks398","article-title":"PepSite: prediction\nof peptide-binding sites from protein surfaces","volume":"40","author":"Trabuco","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2026091511095391000_cit11","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1093\/bioinformatics\/btt278","article-title":"CAPITO--a web server-based analysis\nand plotting tool for circular dichroism data","volume":"29","author":"Wiedemann","year":"2013","journal-title":"Bioinformatics"},{"key":"2026091511095391000_cit12a","doi-asserted-by":"publisher","first-page":"15824","DOI":"10.1073\/pnas.0605629103","article-title":"Generic hydrophobic\nresidues are sufficient to promote aggregation of the Alzheimer\u2019s\nAbeta42 peptide","volume":"103","author":"Kim","year":"2006","journal-title":"Proc. Natl. Acad. Sci. 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Theory Comput."},{"key":"2026091511095391000_cit15c","doi-asserted-by":"publisher","first-page":"W449","DOI":"10.1093\/nar\/gkw329","article-title":"PEP-FOLD3: faster de novo structure\nprediction for linear peptides in solution and in complex","volume":"44","author":"Lamiable","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2026091511095391000_cit16a","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/S0065-7743(08)60900-8","article-title":"Chapter\n30. Peptide Stability in\nDrug Development: in vitro Peptide Degradation in Plasma and Serum","volume":"28","author":"Powell","year":"1993","journal-title":"Annu. Rep. Med. Chem."},{"key":"2026091511095391000_cit16b","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1039\/9781788011532-00001","article-title":"CHAPTER 1:Renaissance in Peptide Drug Discovery: The\nThird Wave, in Peptide-based Drug Discovery: Challenges and New Therapeutics","author":"Sawyer","year":"2017","journal-title":"Drug Discovery"},{"key":"2026091511095391000_cit17a","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1038\/nature08538","article-title":"Multimodal\ntechniques for diagnosis and prognosis of Alzheimer\u2019s disease","volume":"461","author":"Perrin","year":"2009","journal-title":"Nature"},{"key":"2026091511095391000_cit17b","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1177\/1756285611404470","article-title":"Disease-modifying treatments for\nAlzheimer\u2019s disease","volume":"4","author":"Galimberti","year":"2011","journal-title":"Ther. Adv. Neurol.\nDisord."},{"key":"2026091511095391000_cit17c","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1177\/1756285612461679","article-title":"Current\nand future treatments for Alzheimer\u2019s disease","volume":"6","author":"Yiannopoulou","year":"2013","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"2026091511095391000_cit17d","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1146\/annurev-med-042915-103753","article-title":"Update on Alzheimer\u2019s\nDisease Therapy and Prevention Strategies","volume":"68","author":"Graham","year":"2017","journal-title":"Annu.\nRev. Med."},{"key":"2026091511095391000_cit18","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1039\/C6CC08086C","article-title":"A peptide-based synthetic\ntranscription factor selectively down-regulates\nthe proto-oncogene CFOS in tumour cells and inhibits proliferation","volume":"53","author":"Chakraborty","year":"2016","journal-title":"Chem. Commun."},{"key":"2026091511095391000_cit19","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1111\/j.1471-4159.2005.03407.x","article-title":"Globular amyloid\nbeta-peptide oligomer - a homogenous and stable neuropathological\nprotein in Alzheimer\u2019s disease","volume":"95","author":"Barghorn","year":"2005","journal-title":"J. Neurochem."},{"key":"2026091511095391000_cit20","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.bbrc.2015.11.018","article-title":"Solvent exposure of Tyr10 as a probe of structural\ndifferences between monomeric and aggregated forms of the amyloid-beta\npeptide","volume":"468","author":"Aran Terol","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026091511095391000_cit21","doi-asserted-by":"publisher","first-page":"2571","DOI":"10.1074\/jbc.M116.744730","article-title":"Tribbles Pseudokinase\n3 Induces Both Apoptosis and\nAutophagy in Amyloid-beta-induced Neuronal Death","volume":"292","author":"Saleem","year":"2017","journal-title":"J. Biol. Chem."},{"key":"2026091511095391000_cit22a","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31808-5","article-title":"Copper mediated amyloid-beta\nbinding to Transthyretin","volume":"8","author":"Ciccone","year":"2018","journal-title":"Sci. Rep."},{"key":"2026091511095391000_cit22b","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201809027","article-title":"High-affinity\ninteractions and signal transduction between Abeta oligomers and TREM2","volume":"10","author":"Lessard","year":"2018","journal-title":"EMBO Mol. 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Theory Comput."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.0c01730","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/26\/16128\/67754433\/acsomega.0c01730.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/26\/16128\/67754433\/acsomega.0c01730.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:52:35Z","timestamp":1789487555000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/5\/26\/16128\/1648017\/Heptameric-Peptide-Interferes-with-Amyloid"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,25]]},"references-count":45,"journal-issue":{"issue":"26","published-online":{"date-parts":[[2020,6,25]]},"published-print":{"date-parts":[[2020,7,7]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.0c01730","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,25]]}}}