30923-00-3Relevant articles and documents
Trehalose diamide glycolipids augment antigen-specific antibody responses in a Mincle-dependent manner
Lynch, Amy T.,Motozono, Chihiro,Foster, Amy J.,Kodar, Kristel,Dangerfield, Emma M.,Yamasaki, Sho,Wedlock, D. Neil,Timmer, Mattie S.M.,Stocker, Bridget L.
, (2021)
Many studies have investigated how trehalose glycolipid structures can be modified to improve their Macrophage inducible C-type lectin (Mincle)-mediated adjuvanticity. However, in all instances, the ester-linkage of α,α?-trehalose to the lipid of choice remained. We investigated how changing this ester-linkage to an amide influences Mincle signalling and agonist activity and demonstrated that Mincle tolerates this functional group change. In in vivo vaccination studies in murine and ovine model systems, using OVA or Mannheimia haemolytica and Mycoplasma ovipneumoniae as vaccine antigens, respectively, it was demonstrated that a representative trehalose diamide glycolipid was able to enhance antibody-specific immune responses. Notably, IgG titres against M. ovipneumoniae were significantly greater when using trehalose dibehenamide (A-TDB) compared to trehalose dibehenate (TDB). This is particularly important as infection with M. ovipneumoniae predisposes sheep to pneumonia.
Amide-linked brartemicin glycolipids exhibit Mincle-mediated agonist activity in vitro
Dangerfield, Emma M.,Lynch, Amy T.,Kodar, Kristel,Stocker, Bridget L.,Timmer, Mattie S.M.
, (2021/11/11)
Lipidated derivatives of the natural product brartemicin show much promise as vaccine adjuvants due to their ability to signal through the Macrophage Inducible C-type Lectin (Mincle). We synthesised three lipophilic amide-linked brartemicin derivatives and compared their agonist activity to that of their ester-linked counterparts in vitro. We demonstrate that the brartemicin amide derivatives activate bone-marrow-derived macrophages (BMDMs) in a Mincle-dependent manner, as evidenced by the production of the pro-inflammatory cytokine IL-1β in wildtype but not Mincle-/- cells. The amide derivatives showed activity that was as good as, if not better than, their ester counterparts. Two of the amide derivatives, but none of the ester-derivatives, also led to the production of IL-1β by human-derived monocytes. As the production of IL-1β is a good indicator of vaccine adjuvanticity potential, these findings suggest that amide-linked brartemicin derivatives show particular promise as vaccine adjuvants.
α,α-Trehalose derivatives bearing guanidino groups as inhibitors to HIV-1 Tat-TAR RNA interaction in human cells
Wang, Min,Xu, Zhidong,Tu, Pengfei,Yu, Xiaolin,Xiao, Sulong,Yang, Ming
, p. 2585 - 2588 (2007/10/03)
Replication of HIV-1 requires specific interactions of Tat protein with TAR RNA. Disruption of Tat-TAR RNA interaction could inhibit HIV-1 replication. Here four target compounds were designed and synthesized to bind to TAR RNA for blocking the interaction of Tat-TAR RNA. The core molecule 6,6 ′-diamino-6,6′-dideoxy-α,α- trehalose was obtained from selective bromination of, α,α-trehalose at C-6,6′, followed by acetylation, azide displacement, deacetylation, and reduction. Coupling of the core molecule with the protected amino acid, then deprotection and guanidinylation generated the novel α,α-trehalose derivatives. Their abilities to inhibit Tat-TAR RNA interaction in human cells were determined by a Tat-dependent HIV-1 LTR-driven CAT assays.
