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dc.contributor.authorSalunke, Deepak B.
dc.contributor.authorConnelly, Seth W.
dc.contributor.authorShukla, Nikunj M.
dc.contributor.authorHermanson, Alec R.
dc.contributor.authorFox, Lauren M.
dc.contributor.authorDavid, Sunil A.
dc.identifier.citationSalunke, D. B., Connelly, S. W., Shukla, N. M., Hermanson, A. R., Fox, L. M., & David, S. A. (2013). Design and Development of Stable, Water-soluble, Human Toll-like Receptor 2-Specific, Monoacyl Lipopeptides as Candidate Vaccine Adjuvants. Journal of Medicinal Chemistry, 56(14), 10.1021/jm400620g.
dc.description.abstractAntigens in modern subunit vaccines are largely soluble and poorly immunogenic proteins inducing relatively short-lived immune responses. Appropriate adjuvants initiate early innate immune responses, amplifying subsequent adaptive immune responses. Agonists of TLR2 are devoid of significant pro-inflammatory activity in ex vivo human blood models, and yet potently adjuvantic, suggesting that this chemotype may be a safe and effective adjuvant. Our earlier work on the monoacyl lipopeptide class of TLR2 agonists led to the design of a highly potent lead, but with negligible aqueous solubility, necessitating the reintroduction of aqueous solubility. We explored several strategies of introducing ionizable groups on the lipopeptide, as well as the systematic evaluation of chemically stable bioisosteres of the ester-linked palmitoyl group. These studies have led to a fully optimized, chemically stable, and highly water-soluble, human TLR2-specific agonist, which was found to have an excellent safety profile and displayed prominent adjuvantic activities in rabbit models.en_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
dc.subjectTLR2 agonistsen_US
dc.subjectVaccine adjuvantsen_US
dc.subjectInnate immunityen_US
dc.titleDesign and Development of Stable, Water-soluble, Human Toll-like Receptor 2-Specific, Monoacyl Lipopeptides as Candidate Vaccine Adjuvantsen_US
kusw.kuauthorSalunke, Deepak B.
kusw.kuauthorConnelly, Seth W.
kusw.kuauthorShukla, Nikunj M.
kusw.kuauthorHermanson, Alex R.
kusw.kuauthorFox, Lauren M.
kusw.kuauthorDavid, Sunil A.
kusw.kudepartmentMedicinal Chemistryen_US
kusw.oanotesPer SHERPA/RoMEO 4/6/2017: Author's Pre-print: grey tick subject to Restrictions below, author can archive pre-print (ie pre-refereeing) Restrictions:

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kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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