dc.creator | González Cuesta, Manuel | es |
dc.creator | Lai, Alan Chuan Ying | es |
dc.creator | Chi, Po Yu | es |
dc.creator | Hsu, I. Ling | es |
dc.creator | Liu, Nien Tzu | es |
dc.creator | Wu, Ko Chien | es |
dc.creator | García Fernández, José Manuel | es |
dc.creator | Ortiz Mellet, Carmen | es |
dc.date.accessioned | 2023-05-10T08:43:06Z | |
dc.date.available | 2023-05-10T08:43:06Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | González Cuesta, M., Lai, A.C.Y., Chi, P.Y., Hsu, I.L., Liu, N.T., Wu, K.C.,...,Ortiz Mellet, C. (2023). Serine-/Cysteine-based sp2-Iminoglycolipids as novel TLR4 agonists: evaluation of their adjuvancy and immunotherapeutic properties in a murine model of asthma. Journal of Medicinal Chemistry, 66 (7), 4768-4783. https://doi.org/10.1021/acs.jmedchem.2c01948. | |
dc.identifier.issn | 0022-2623 | es |
dc.identifier.issn | 1520-4804 | es |
dc.identifier.uri | https://hdl.handle.net/11441/145759 | |
dc.description.abstract | Glycolipids with TLR4 agonistic properties can serve either as therapeutic agents or as vaccine adjuvants by stimulating the development of proinflammatory responses. Translating them to the clinical setting is hampered by synthetic difficulties, the lack of stability in biological media, and/or a suboptimal profile of balanced immune mediator secretion. Here, we show that replacement of the sugar fragment by an sp2-iminosugar moiety in a prototypic TLR4 agonist, CCL-34, yields iminoglycolipid analogues that retain or improve their biological activity in vitro and in vivo and can be accessed through scalable protocols with total stereoselectivity. Their adjuvant potential is manifested in their ability to induce the secretion of proinflammatory cytokines, prime the maturation of dendritic cells, and promote the proliferation of CD8+ T cells, pertaining to a Th1-biased profile. Additionally, their therapeutic potential for the treatment of asthma, a Th2-dominated inflammatory pathology, has been confirmed in an ovalbumin-induced airway hyperreactivity mouse model. | es |
dc.description.sponsorship | Ministerio de Ciencia e Innovación y Agencia Estatal de Investigación, de España MCIN/AEI y Fondos Europeos FEDER - PID2019-105858RB-I00, RTI2018- 097609-B-C21 y PID2021-124247OB-C21 | es |
dc.description.sponsorship | Junta de Andalucía - P20_00166 | es |
dc.description.sponsorship | Ministry of Science and Technology de Taiwan - 111-2320-B-001-025-MY3 | es |
dc.format | application/pdf | es |
dc.format.extent | 16 p. | es |
dc.language.iso | eng | es |
dc.publisher | American Chemical Society | es |
dc.relation.ispartof | Journal of Medicinal Chemistry, 66 (7), 4768-4783. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | Serine-/Cysteine-based sp2-Iminoglycolipids as novel TLR4 agonists: evaluation of their adjuvancy and immunotherapeutic properties in a murine model of asthma | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Química orgánica | es |
dc.relation.projectID | PID2019-105858RB-I00 | es |
dc.relation.projectID | RTI2018- 097609-B-C21 | es |
dc.relation.projectID | PID2021-124247OB-C21 | es |
dc.relation.projectID | P20_00166 | es |
dc.relation.projectID | 111-2320-B-001-025-MY3 | es |
dc.relation.publisherversion | https://doi.org/10.1021/acs.jmedchem.2c01948 | es |
dc.identifier.doi | 10.1021/acs.jmedchem.2c01948 | es |
dc.journaltitle | Journal of Medicinal Chemistry | es |
dc.publication.volumen | 66 | es |
dc.publication.issue | 7 | es |
dc.publication.initialPage | 4768 | es |
dc.publication.endPage | 4783 | es |
dc.contributor.funder | Ministerio de Ciencia e Innovación (MICIN). España | es |
dc.contributor.funder | Agencia Estatal de Investigación. España | es |
dc.contributor.funder | Junta de Andalucía | es |
dc.contributor.funder | Gobierno de Taiwán | es |