Discovery of nitric oxide-inducing activities of synthetic LAM glycan motifs prepared by scalable rapid syntheses. (15th November 2022)

• Record Type: Journal Article
• Authors: Suwanwong, Nutchapong; Chatwichien, Jaruwan; Chainok, Kittipong; Ruchirawat, Somsak; Boonyarattanakalin, Siwarutt
• Is Part Of: Carbohydrate polymers. Volume 296(2022)
• Publication Date: 2022-11-15
• Subjects: ManLAM mannose-capped lipoarabinomannan -- LAM lipoarabinomannan -- LPS lipopolysaccharide -- NO nitric oxide -- Mtb Mycobacterium tuberculosis; Lipoarabinomannan -- Rapid synthesis -- Arabinan -- Mannan -- Synthetic glycan -- Nitric oxide; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2022.119637
• Languages: English
• ISSNs: 0144-8617

Abstract

Abstract: Enhancement of local nitric oxide (NO) concentration is important for the effectiveness of an adjuvant and for both innate and adaptive immunological responses. Currently, the information on the NO-inducing activities of lipoarabinomannan (LAM) glycan motifs on Mycobacterium tuberculosis ( Mtb ) is not possibly available. Thus, detailed studies on the structure-activity relationship of discrete LAM glycan motifs could provide valuable information towards the development of adjuvants and vaccines against Mtb . Using the newly-designed monomers and linker, the new rapid synthesis strategies demonstrated in this work enabled accessibilities to α(1→6)-D -mannans and α(1→5)-D -arabinans, which are the key LAM glycan motifs, with different controlled-sizes, in a scalable fashion. The glycans were evaluated for their ability to co-stimulate nitric oxide in macrophages. Only short and medium α(1→5)-D -arabinans show distinct abilities to strongly enhance LPS-induced nitric oxide, suggesting their potential use as stronger immunomodulators than α(1→6)-D -mannans, and thus, implying an unknown receptor responsible for this NO-inducing effect. Graphical abstract: Unlabelled Image Highlights: Short and medium arabinans strongly enhance LPS-induced nitric oxide production. Mannans and long arabinan did not enhance LPS-induced nitric oxide production. New monomers were designed and their syntheses were optimized for scalability. LAM glycans with amine linker made in gram scales by controlled rapid syntheses.