Show simple item record

dc.contributor.authorBarata, T.
dc.contributor.authorTeo, I.
dc.contributor.authorLalwani, S.
dc.contributor.authorSimanek, E.
dc.contributor.authorZloh, Mire
dc.contributor.authorShaunak, S.
dc.date.accessioned2013-04-24T13:50:04Z
dc.date.available2013-04-24T13:50:04Z
dc.date.issued2011-11-01
dc.identifier.citationBarata , T , Teo , I , Lalwani , S , Simanek , E , Zloh , M & Shaunak , S 2011 , ' Computational design principles for bioactive dendrimer based constructs as antagonists of the TLR4-MD-2-LPS complex ' , Biomaterials , vol. 32 , no. 33 , pp. 8702-8711 . https://doi.org/10.1016/j.biomaterials.2011.07.085
dc.identifier.issn0142-9612
dc.identifier.otherPURE: 1459015
dc.identifier.otherPURE UUID: 0ba4ee49-0ef6-4021-bb31-098b5bd46630
dc.identifier.otherScopus: 80052967040
dc.identifier.urihttp://hdl.handle.net/2299/10492
dc.descriptionMEDLINE® is the source for the MeSH terms of this document.
dc.description.abstractThe cell surface interaction between bacterial lipopolysaccharide (LPS), Toll-like receptor 4 (TLR4) and MD-2 is central to bacterial sepsis syndromes and wound healing. We have shown that a generation (G) 3.5 polyamidoamine (PAMAM) dendrimer that was partially glycosylated with glucosamine inhibits TLR4-MD-2-LPS induced inflammation in a rabbit model of tissue scaring. However, it was a mixture of closely related chemical species because of the polydispersity of the starting PAMAM dendrimer. Generation 2 triazine dendrimers with single chemical entity material status are available at low cost and at the kilogram scale. PAMAM dendrimer can be synthetically grafted onto this triazine core dendrimer to make new triazine-PAMAM hybrid dendrimers. This led us to examine whether molecular modelling methods could be used to identify the key structural design principles for a bioactive lead molecule that could be synthesized and biologically evaluated. We describe our computer aided molecular studies of several dendrimer based constructs and the key design principles identified. Our approach should be more broadly applicable to the biologically focused, rational and accelerated design of molecules for other TLR receptors. They could be useful for treating infectious, inflammatory and malignant diseases.en
dc.format.extent10
dc.language.isoeng
dc.relation.ispartofBiomaterials
dc.titleComputational design principles for bioactive dendrimer based constructs as antagonists of the TLR4-MD-2-LPS complexen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionDepartment of Pharmacy
dc.contributor.institutionMedicinal and Analytical Chemistry
dc.description.statusPeer reviewed
rioxxterms.versionofrecordhttps://doi.org/10.1016/j.biomaterials.2011.07.085
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record