Open Access Te Herenga Waka-Victoria University of Wellington
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Trehalose amide glycolipids as Mincle ligands: Towards new vaccine adjuvants

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posted on 2021-12-09, 11:55 authored by Amy Lynch

The development of new vaccines to respond to infectious diseases requires new vaccine adjuvants, which improve vaccine efficacy and shape the immune response. Trehalose glycolipids, consisting of α,α'-trehalose esterified at the 6- and 6'- positions with lipids, exhibit adjuvant activity by binding and activating Macrophage inducible C-type lectin (Mincle). However, the adjuvant activity of trehalose glycolipids could potentially be improved by substituting the ester linkages for more physiologically stable amide bonds. This thesis presents a short protecting group free route to trehalose amide glycolipids, thus allowing for the synthesis of the straight chain glycolipid amides 1a-e in four steps and in excellent (53-61%) overall yields (Figure 1). Amide glycolipids 1a-e were demonstrated to be Mincle agonists with comparable activity to their ester counterparts, as determined using a green fluorescent protein (GFP) reporter cell line assay. A second generation of trehalose amide glycolipids, the lipidated brartemicin amide analogues 2a-c, were subsequently synthesised (Figure 1). This report is the first example of trehalose amide glycolipids acting as Mincle agonists, and further studies into the potential of the amides as vaccine adjuvants will be undertaken in due course.


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Te Herenga Waka—Victoria University of Wellington

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Te Herenga Waka—Victoria University of Wellington

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Degree Name

Master of Science

ANZSRC Type Of Activity code

970103 Expanding Knowledge in the Chemical Sciences

Victoria University of Wellington Item Type

Awarded Research Masters Thesis



Victoria University of Wellington School

School of Chemical and Physical Sciences


Stocker, Bridget; Timmer, Mattie