Synthesis of asparagine derivatives harboring a Lewis X type DC-SIGN ligand and evaluation of their impact on immunomodulation in multiple sclerosis.

Synthesis of asparagine derivatives harboring a Lewis X type DC-SIGN ligand and evaluation of their impact on immunomodulation in multiple sclerosis.
Chemistry. 2020 Oct 22;:
Authors: Doelman W, Marqvorsen MHS, Chiodo F, Bruijns SCM, van der Marel GA, van Kooyk Y, van Kasteren SI, Araman C
Abstract
The protein myelin oligodendrocyte glycoprotein (MOG) is a key component of myelin and an autoantigen in the disease multiple sclerosis (MS). The posttranslational N-glycosylation of Asn31 of MOG seems to play a key role in modulating the immune response towards myelin. This is mediated by the interaction of Lewis type glycan structures on the N-glycan of MOG to the DC-SIGN receptor on dendritic cells (DCs). Here, we report the synthesis of an unnatural Lewis X (LeX) containing Fmoc-SPPS compatible asparagine building block, as well as asparagine building blocks containing two LeX derived oligosaccharides: LacNAc and Fucα1-3GlcNAc. These building blocks were utilized for the synthesis of glycosylated MOG (MOG31-55) and were analyzed with respect to their ability to bind to DC-SIGN in different biological setups, as well as their ability to inhibit the citrullination induced aggregation of MOG31-55. Finally, a cytokine secretion assay was carried out on human moDCs, showing the ability of a neoglycopeptide decorated with a single LeX to alter the balance of pro- and antiinflammatory cytokines, inducing a tolerogenic response.
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Source: Chemistry - October 22, 2020 Category: Chemistry Authors: Doelman W, Marqvorsen MHS, Chiodo F, Bruijns SCM, van der Marel GA, van Kooyk Y, van Kasteren SI, Araman C Tags: Chemistry Source Type: research