Synthesis of N-Glycolylneuraminic Acid (Neu5Gc) and Its Glycosides

Abstract

Sialic acids constitute a family of negatively charged structurally diverse monosaccharides that are commonly presented on the termini of glycans in higher animals and some microorganisms. In addition to N -acetylneuraminic acid (Neu5Ac), N -glycolyl neuraminic acid (Neu5Gc) is among the most common sialic acid forms in nature. Nevertheless, unlike most animals, human cells loss the ability to synthesize Neu5Gc although Neu5Gc-containing glycoconjugates have been found on human cancer cells and in various human tissues due to dietary incorporation of Neu5Gc. Some pathogenic bacteria also produce Neu5Ac and the corresponding glycoconjugates but Neu5Gc-producing bacteria have yet to be found. In addition to Neu5Gc, more than 20 Neu5Gc derivatives have been found in non-human vertebrates. To explore the biological roles of Neu5Gc and its naturally occurring derivatives as well as the corresponding glycans and glycoconjugates, various chemical and enzymatic synthetic methods have been developed to obtain a vast array of glycosides containing Neu5Gc and/or its derivatives. Here we provide an overview on various synthetic methods that have been developed. Among these, the application of highly efficient one-pot multienzyme (OPME) sialylation systems in synthesizing compounds containing Neu5Gc and derivatives has been proven as a powerful strategy.

Correlation of serum N-Acetylneuraminic acid with the risk and prognosis of acute coronary syndrome: a prospective cohort study

“…N-acetylneuraminic acid (Neu5Ac) is one of the commonly distributed natural carbohydrates, and it is also a basic component of many glycoproteins, including glycopeptides and glycolipids, with a wide range of biological functions [12]. Moreover, the biochemical derivatives of Neu5Ac are also commonly used in the synthesis of medications [12]. Recent studies showed that Neu5Ac may participate in the pathogenesis of atherosclerosis by promoting immune inflammatory response [13,14], regulating lipoprotein metabolism [15], enhancing insulin resistance [16], accelerating thrombosis formation [17], and stimulating vascular smooth muscle cell proliferation and apoptosis [18].…”

“…Therefore, detection of some metabolites may be helpful for clarifying the pathophysiological mechanism of the disease [ 11 ]. N-acetylneuraminic acid (Neu5Ac) is one of the commonly distributed natural carbohydrates, and it is also a basic component of many glycoproteins, including glycopeptides and glycolipids, with a wide range of biological functions [ 12 ]. Moreover, the biochemical derivatives of Neu5Ac are also commonly used in the synthesis of medications [ 12 ].…”

Challenging the Role of Diet-Induced Anti-Neu5Gc Antibodies in Human Pathologies

“…Few studies have investigated Neu5Gc loading among human cells (8,9); however, further studies are warranted to establish whether indeed a substantial fraction of humans actually lack the fundamental component of the theoretical basis of the xenosialitis model. Although Neu5Gc exists at trace levels on ECs of positive individuals, we must also consider the myriad of surface glycoproteins or lipoproteins that display Neu5Gc and the high diversity of Neu5Gc terminal residues, which result in a huge dispersion of cell-surface epitopes that are potentially recognized by A-GcAbs (15). It is thus possible that, following interactions with A-GcAbs, the coexistence of trace levels of antigens and the high epitope dispersion results in physiological cellular signaling that is below the activation threshold.…”

Natural and Synthetic Sialylated Glycan Microarrays and Their Applications

“…The most extensive variety of sialosides, containing Ac and Gc forms as well as other modifications, for use on microarrays and in other applications has been derived by the laboratory of Xi Chen (Yu et al, 2005, 2006a,b, 2011; Chokhawala et al, 2008; Linman et al, 2012; Khedri et al, 2014; Li et al, 2017). This work uses novel one-pot synthesis and combinatorial methods, and is the subject of another review in this issue (Chen et al, 2019). The diversity and biological applications of large libraries of natural and non-natural sialosides and their chemical approaches were well described in previous reviews (Deng et al, 2013; Liang et al, 2015).…”