Synthesis and Evaluation of Novel TLR2 Agonists as Potential Adjuvants for Cancer Vaccines

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dc.contributor.author Lu, Benjamin en
dc.contributor.author Williams, Geoffrey en
dc.contributor.author Verdon, DJ en
dc.contributor.author Dunbar, Peter en
dc.contributor.author Brimble, Margaret en
dc.date.accessioned 2019-10-29T00:13:39Z en
dc.date.issued 2019 en
dc.identifier.issn 0022-2623 en
dc.identifier.uri http://hdl.handle.net/2292/48666 en
dc.description.abstract Cancer immunotherapy has gained increasing attention due to its potential specificity and lack of adverse side effects when compared to more traditional modes of treatment. Toll-like receptor 2 (TLR2) agonists are lipopeptides possessing the S-[2,3-bis(palmitoyloxy)propyl]-l-cysteine (Pam2Cys) motif and exhibit potent immunostimulatory effects. These agonists offer a means of providing “danger signals” in order to activate the immune system toward tumor antigens. Thus, the development of TLR2 agonists is attractive in the search of potential immunostimulants for cancer. Existing SAR studies of Pam2Cys with TLR2 indicate that the structural requirements for activity are, for the most part, very intolerable. We have investigated the importance of stereochemistry, the effect of N-terminal acylation, and homologation between the two ester functionalities in Pam2Cys-conjugated lipopeptides on TLR2 activity. The R diastereomer is significantly more potent than the S diastereomer and N-terminal modification generally lowers TLR2 activity. Most notably, homologation gives rise to analogues which are comparatively active to the native Pam2Cys containing constructs. en
dc.publisher American Chemical Society en
dc.relation.ispartofseries Journal of Medicinal Chemistry en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Synthesis and Evaluation of Novel TLR2 Agonists as Potential Adjuvants for Cancer Vaccines en
dc.type Journal Article en
dc.identifier.doi 10.1021/acs.jmedchem.9b01044 en
dc.rights.holder Copyright: The author en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 780583 en
pubs.org-id Science en
pubs.org-id Biological Sciences en
pubs.org-id Chemistry en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
pubs.record-created-at-source-date 2019-09-11 en
pubs.online-publication-date 2019-08-16 en
pubs.dimensions-id 31418565 en


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