{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T23:22:52Z","timestamp":1780615372909,"version":"3.54.1"},"reference-count":54,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,8,17]],"date-time":"2018-08-17T00:00:00Z","timestamp":1534464000000},"content-version":"vor","delay-in-days":381,"URL":"https:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-74493"],"award-info":[{"award-number":["MOP-74493"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Foundation for Innovation"},{"name":"Michael Smith Foundation"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Chemical Biology"],"published-print":{"date-parts":[[2017,8]]},"DOI":"10.1016\/j.chembiol.2017.07.010","type":"journal-article","created":{"date-parts":[[2017,8,10]],"date-time":"2017-08-10T18:00:37Z","timestamp":1502388037000},"page":"969-980.e4","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":59,"title":["Aggregation and Its Influence on the Immunomodulatory Activity of Synthetic Innate Defense Regulator Peptides"],"prefix":"10.1016","volume":"24","author":[{"given":"Evan F.","family":"Haney","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing (Catherine)","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley L.","family":"Hilchie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.W.","family":"Hancock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.chembiol.2017.07.010_bib1","doi-asserted-by":"crossref","first-page":"135ra64","DOI":"10.1126\/scitranslmed.3003515","article-title":"Effective adjunctive therapy by an innate defense regulatory peptide in a preclinical model of severe malaria","volume":"4","author":"Achtman","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.chembiol.2017.07.010_bib2","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nrd3050","article-title":"Protein aggregation diseases: pathogenicity and therapeutic perspectives","volume":"9","author":"Aguzzi","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.chembiol.2017.07.010_bib3","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1111\/j.1742-4658.2008.06554.x","article-title":"Structural requirements for antimicrobial versus chemoattractant activities for dermaseptin S9","volume":"275","author":"Auvynet","year":"2008","journal-title":"FEBS J."},{"key":"10.1016\/j.chembiol.2017.07.010_bib4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1042\/bse0560041","article-title":"Predicting aggregation-prone sequences in proteins","volume":"56","author":"Baets","year":"2014","journal-title":"Essays Biochem."},{"key":"10.1016\/j.chembiol.2017.07.010_bib5","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1111\/mmi.13269","article-title":"Protein aggregation as an antibiotic design strategy","volume":"99","author":"Bednarska","year":"2016","journal-title":"Mol. Microbiol."},{"key":"10.1016\/j.chembiol.2017.07.010_bib6","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/ana.24087","article-title":"Innate defense regulator peptide 1018 protects against perinatal brain injury","volume":"75","author":"Bolouri","year":"2014","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.chembiol.2017.07.010_bib7","doi-asserted-by":"crossref","first-page":"6760","DOI":"10.1021\/acs.biochem.5b00813","article-title":"A spectroscopic study of the aggregation state of the human antimicrobial peptide LL-37 in bacterial versus host cell model membranes","volume":"54","author":"Bonucci","year":"2015","journal-title":"Biochemistry"},{"key":"10.1016\/j.chembiol.2017.07.010_bib8","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.bpc.2005.05.010","article-title":"Why forces between proteins follow different Hofmeister series for pH above and below pI","volume":"117","author":"Bostr\u00f6m","year":"2005","journal-title":"Biophys. Chem."},{"key":"10.1016\/j.chembiol.2017.07.010_bib9","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1189\/jlb.0704380","article-title":"Impact of LL-37 on anti-infective immunity","volume":"77","author":"Bowdish","year":"2005","journal-title":"J.\u00a0Leukoc. Biol."},{"key":"10.1016\/j.chembiol.2017.07.010_bib10","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/416507a","article-title":"Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases","volume":"416","author":"Bucciantini","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.chembiol.2017.07.010_bib11","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/nature01891","article-title":"Rationalization of the effects of mutations on peptide and protein aggregation rates","volume":"424","author":"Chiti","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.chembiol.2017.07.010_bib12","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/1471-2105-8-65","article-title":"AGGRESCAN: a server for the prediction and evaluation of \u201chot spots\u201d of aggregation in polypeptides","volume":"8","author":"Conchillo-Sol\u00e9","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.chembiol.2017.07.010_bib13","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1128\/JB.155.2.831-838.1983","article-title":"Procedure for isolation of bacterial lipopolysaccharides from both smooth and rough Pseudomonas aeruginosa and Salmonella typhimurium strains","volume":"155","author":"Darveau","year":"1983","journal-title":"J.\u00a0Bacteriol."},{"key":"10.1016\/j.chembiol.2017.07.010_bib14","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1038\/nature02261","article-title":"Protein folding and misfolding","volume":"426","author":"Dobson","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.chembiol.2017.07.010_bib15","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.sbi.2014.12.004","article-title":"Inhibition of protein aggregation and amyloid formation by small molecules","volume":"30","author":"Doig","year":"2015","journal-title":"Curr. Opin. Struct. Biol."},{"key":"10.1016\/j.chembiol.2017.07.010_bib16","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1021\/bm500169p","article-title":"Drug carriers for the delivery of therapeutic peptides","volume":"15","author":"Du","year":"2014","journal-title":"Biomacromolecules"},{"key":"10.1016\/j.chembiol.2017.07.010_bib17","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nrd4593","article-title":"Targeting protein aggregation for the treatment of degenerative diseases","volume":"14","author":"Eisele","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.chembiol.2017.07.010_bib18","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nrd3591","article-title":"Designing antimicrobial peptides: form follows function","volume":"11","author":"Fjell","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.chembiol.2017.07.010_bib19","doi-asserted-by":"crossref","first-page":"10105","DOI":"10.1073\/pnas.0501215102","article-title":"Rational design of aggregation-resistant bioactive peptides: reengineering human calcitonin","volume":"102","author":"Fowler","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.chembiol.2017.07.010_bib20","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nrd1695","article-title":"Protein drug stability: a formulation challenge","volume":"4","author":"Frokjaer","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.chembiol.2017.07.010_bib21","doi-asserted-by":"crossref","first-page":"e1004152","DOI":"10.1371\/journal.ppat.1004152","article-title":"Broad-spectrum anti-biofilm peptide that targets a cellular stress response","volume":"10","author":"de la Fuente-N\u00fa\u00f1ez","year":"2014","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.chembiol.2017.07.010_bib22","doi-asserted-by":"crossref","first-page":"31609","DOI":"10.1074\/jbc.272.50.31609","article-title":"Selective cytotoxicity of dermaseptin S3 toward intraerythrocytic plasmodium falciparum and the underlying molecular basis","volume":"272","author":"Ghosh","year":"1997","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.chembiol.2017.07.010_bib23","first-page":"L347","article-title":"Culture and\u00a0transformation of human airway epithelial cells","volume":"268","author":"Gruenert","year":"1995","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.chembiol.2017.07.010_bib24","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nri.2016.29","article-title":"The immunology of host defence peptides: beyond antimicrobial activity","volume":"16","author":"Hancock","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.chembiol.2017.07.010_bib25","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.peptides.2015.03.015","article-title":"High throughput screening methods for assessing antibiofilm and immunomodulatory activities of synthetic peptides","volume":"71","author":"Haney","year":"2015","journal-title":"Peptides"},{"key":"10.1016\/j.chembiol.2017.07.010_bib26","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1111\/j.1538-7836.2012.04640.x","article-title":"Human neutrophil alpha-defensins induce formation of fibrinogen and thrombospondin-1 amyloid-like structures and activate platelets via glycoprotein IIb\/IIIa","volume":"10","author":"Horn","year":"2012","journal-title":"J.\u00a0Thromb. Haemost."},{"key":"10.1016\/j.chembiol.2017.07.010_bib27","doi-asserted-by":"crossref","first-page":"3718","DOI":"10.1074\/jbc.273.6.3718","article-title":"Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37","volume":"273","author":"Johansson","year":"1998","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.chembiol.2017.07.010_bib28","doi-asserted-by":"crossref","first-page":"15824","DOI":"10.1073\/pnas.0605629103","article-title":"Generic hydrophobic residues are sufficient to promote aggregation of the Alzheimer\u2019s A\u03b242 peptide","volume":"103","author":"Kim","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.chembiol.2017.07.010_bib29","doi-asserted-by":"crossref","first-page":"340ra72","DOI":"10.1126\/scitranslmed.aaf1059","article-title":"Amyloid-\u03b2 peptide protects against microbial infection in mouse and worm models of Alzheimer\u2019s disease","volume":"8","author":"Kumar","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.chembiol.2017.07.010_bib30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2007.05.049","article-title":"Developing early formulations: practice and perspective","volume":"341","author":"Li","year":"2007","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.chembiol.2017.07.010_bib31","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.pep.2007.02.003","article-title":"A novel method for purifying recombinant human host defense cathelicidin LL-37 by utilizing its inherent property of aggregation","volume":"54","author":"Li","year":"2007","journal-title":"Protein Expr. Purif."},{"key":"10.1016\/j.chembiol.2017.07.010_bib32","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/psc.2708","article-title":"Peptide IDR-1018: modulating the immune system and targeting bacterial biofilms to treat antibiotic-resistant bacterial infections","volume":"21","author":"Mansour","year":"2015","journal-title":"J.\u00a0Pept. Sci."},{"key":"10.1016\/j.chembiol.2017.07.010_bib33","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1021\/cr8003828","article-title":"Effect of ions on the structure of water: structure making and breaking","volume":"109","author":"Marcus","year":"2009","journal-title":"Chem. Rev."},{"key":"10.1016\/j.chembiol.2017.07.010_bib34","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.4049\/jimmunol.0802586","article-title":"Intracellular receptor for human host defense peptide LL-37 in monocytes","volume":"183","author":"Mookherjee","year":"2009","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.chembiol.2017.07.010_bib35","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/S0006-291X(02)00670-8","article-title":"Aggregation and neurotoxicity of mutant amyloid \u03b2 (A\u03b2) peptides with proline replacement: importance of turn formation at positions 22 and 23","volume":"295","author":"Morimoto","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.chembiol.2017.07.010_bib36","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tibtech.2011.05.001","article-title":"The expanding scope of antimicrobial peptide structures and their modes of action","volume":"29","author":"Nguyen","year":"2011","journal-title":"Trends Biotechnol."},{"key":"10.1016\/j.chembiol.2017.07.010_bib37","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.4049\/jimmunol.0901813","article-title":"Synthetic cationic peptide IDR-1002 provides protection against bacterial infections through chemokine induction and enhanced leukocyte recruitment","volume":"184","author":"Nijnik","year":"2010","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.chembiol.2017.07.010_bib38","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1189\/jlb.1012497","article-title":"The innate defense regulator peptides IDR-HH2, IDR-1002, and IDR-1018 modulate human neutrophil functions","volume":"94","author":"Niyonsaba","year":"2013","journal-title":"J.\u00a0Leukoc. Biol."},{"key":"10.1016\/j.chembiol.2017.07.010_bib39","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1042\/bj3410501","article-title":"Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity","volume":"341","author":"Oren","year":"1999","journal-title":"Biochem. J."},{"key":"10.1016\/j.chembiol.2017.07.010_bib40","doi-asserted-by":"crossref","first-page":"e52449","DOI":"10.1371\/journal.pone.0052449","article-title":"Synthetic cationic peptide IDR-1018 modulates human macrophage differentiation","volume":"8","author":"Pena","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.chembiol.2017.07.010_bib41","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3109\/1547691X.2013.821564","article-title":"Immunogenicity of therapeutic proteins: influence of aggregation","volume":"11","author":"Ratanji","year":"2014","journal-title":"J.\u00a0Immunotoxicol"},{"key":"10.1016\/j.chembiol.2017.07.010_bib42","series-title":"Prediction of Protein Structure and the Principles of Protein Conformation","first-page":"1","article-title":"Principles and patterns of protein conformation","author":"Richardson","year":"1989"},{"key":"10.1016\/j.chembiol.2017.07.010_bib43","doi-asserted-by":"crossref","first-page":"e59119","DOI":"10.1371\/journal.pone.0059119","article-title":"Ability of innate defence regulator peptides IDR-1002, IDR-HH2 and IDR-1018 to protect against Mycobacterium tuberculosis infections in animal models","volume":"8","author":"Rivas-Santiago","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.chembiol.2017.07.010_bib44","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.tibtech.2014.05.005","article-title":"Therapeutic protein aggregation: mechanisms, design, and control","volume":"32","author":"Roberts","year":"2014","journal-title":"Trends Biotechnol."},{"key":"10.1016\/j.chembiol.2017.07.010_bib45","doi-asserted-by":"crossref","first-page":"4308","DOI":"10.1128\/AAC.00656-08","article-title":"Impact of self-assembly properties on antibacterial activity of short acyl-lysine oligomers","volume":"52","author":"Sarig","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.chembiol.2017.07.010_bib46","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/nprot.2006.4","article-title":"Tricine-SDS-PAGE","volume":"1","author":"Sch\u00e4gger","year":"2006","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.chembiol.2017.07.010_bib47","doi-asserted-by":"crossref","first-page":"38184","DOI":"10.1038\/srep38184","article-title":"Membrane core-specific antimicrobial action of cathelicidin LL-37 peptide switches between pore and nanofibre formation","volume":"6","author":"Shahmiri","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.chembiol.2017.07.010_bib48","doi-asserted-by":"crossref","first-page":"e9505","DOI":"10.1371\/journal.pone.0009505","article-title":"The Alzheimer\u2019s disease-associated amyloid \u03b2-protein is an antimicrobial peptide","volume":"5","author":"Soscia","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.chembiol.2017.07.010_bib49","doi-asserted-by":"crossref","first-page":"e39373","DOI":"10.1371\/journal.pone.0039373","article-title":"Innate defense regulator peptide 1018 in wound healing and wound infection","volume":"7","author":"Steinstraesser","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.chembiol.2017.07.010_bib50","doi-asserted-by":"crossref","first-page":"10686","DOI":"10.1002\/anie.201103589","article-title":"The generation of antimicrobial peptide activity: a trade-off between charge and aggregation?","volume":"50","author":"Torrent","year":"2011","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.chembiol.2017.07.010_bib51","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.chembiol.2010.07.007","article-title":"Structural studies of a peptide with immune modulating and direct antimicrobial activity","volume":"17","author":"Wieczorek","year":"2010","journal-title":"Chem. Biol."},{"key":"10.1016\/j.chembiol.2017.07.010_bib52","doi-asserted-by":"crossref","first-page":"36007","DOI":"10.1074\/jbc.C109.073627","article-title":"Sequestosome-1\/p62 is the key intracellular target of innate defense regulator peptide","volume":"284","author":"Yu","year":"2009","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.chembiol.2017.07.010_bib53","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jconrel.2011.08.029","article-title":"PEG-stabilized lipid disks as carriers for amphiphilic antimicrobial peptides","volume":"156","author":"Zetterberg","year":"2011","journal-title":"J.\u00a0Controlled Release"},{"key":"10.1016\/j.chembiol.2017.07.010_bib54","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.cbpa.2006.09.020","article-title":"Interactions between macromolecules and ions: the Hofmeister series","volume":"10","author":"Zhang","year":"2006","journal-title":"Curr. Opin. Chem. Biol."}],"container-title":["Cell Chemical Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S245194561730243X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S245194561730243X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T20:59:20Z","timestamp":1602709160000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S245194561730243X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8]]},"references-count":54,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["S245194561730243X"],"URL":"https:\/\/doi.org\/10.1016\/j.chembiol.2017.07.010","relation":{},"ISSN":["2451-9456"],"issn-type":[{"value":"2451-9456","type":"print"}],"subject":[],"published":{"date-parts":[[2017,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Aggregation and Its Influence on the Immunomodulatory Activity of Synthetic Innate Defense Regulator Peptides","name":"articletitle","label":"Article Title"},{"value":"Cell Chemical Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.chembiol.2017.07.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}