Sialic Acids as Receptors for Pathogens

Abstract

Carbohydrates have long been known to mediate intracellular interactions, whether within one organism or between different organisms. Sialic acids (Sias) are carbohydrates that usually occupy the terminal positions in longer carbohydrate chains, which makes them common recognition targets mediating these interactions. In this review, we summarize the knowledge about animal disease-causing agents such as viruses, bacteria and protozoa (including the malaria parasite Plasmodium falciparum) in which Sias play a role in infection biology. While Sias may promote binding of, e.g., influenza viruses and SV40, they act as decoys for betacoronaviruses. The presence of two common forms of Sias, Neu5Ac and Neu5Gc, is species-specific, and in humans, the enzyme converting Neu5Ac to Neu5Gc (CMAH, CMP-Neu5Ac hydroxylase) is lost, most likely due to adaptation to pathogen regimes; we discuss the research about the influence of malaria on this trait. In addition, we present data suggesting the CMAH gene was probably present in the ancestor of animals, shedding light on its glycobiology. We predict that a better understanding of the role of Sias in disease vectors would lead to more effective clinical interventions.

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

“…Deprotected sugars (final products) were lyophilised using a Buchi Lyovapor L-200 freeze dryer. 1 H, COSY, 13 C, DEPT-135 and HSQC NMR spectra were recorded on a Bruker Avance III 400 MHz at 298 K. Chemical shifts (δ) recorded in CDCl3 and D2O are reported with respect to the solvent residual peak at 7.26 and 4.79 ppm in 1 H NMR, respectively. High resolution mass spectra were acquired using electrospray ionisation in a Waters Vion with Waters Acquity LCMS (positive mode).…”

“…The organic layer was dried over MgSO4, filtered, concentrated under vacuum and purified by flash chromatography [cartridge: SNAP Ultra 10g; gradient: 50-100% EtOAc/Hexane (v:v); flow: 12 mL/min] to afford compound 1 as a white solid with 72% yield (370 mg; 0.72 mmol). 1 = 4.8 Hz, H-3eq), 2.14 (3H, s, CH3CO), 2.12 (3H, s, CH3CO), 2.03 (6H, s, 2x CH3CO), 1.88 (3H, s, CH3CONH), 1.87-1.79 (1H, m, H-3ax). 13 C NMR (101 MHz, CDCl3) δ 170.9, 170.7, 170.4, 170.2, 170.1 (4x CH3CO, C-1), 167.2 (CH3CONH), 89.1 (C-2), 74.1 (C-6), 69.6 (C-8), 68.9 (C-4), 67.6 (C-7), 62.2 (C-9), 53.6 (CO2CH3), 49.4 (C-5), 36.7 (C-3), 23.3 (CH3CONH), 21.1, 20.9, 20.8, 20.8 (4x CH3CO).…”

“…Yield: 70% (28 mg; 0.041 mmol). 1 H NMR (400 MHz, CDCl3) δ 8.15 (1H, s, CHtriazole), 7.88 (1H, d, J = 7.7 Hz, H-Ph), 7.76 (1H, dd, J = 8.0 Hz, J =1. 3 Hz, H-Ph), 7.63 (1H, td, J = 7.7, 1.3 Hz, H-Ph), 7.50 (1H, t, J = 7.7 Hz, H-Ph), 5.47-5.37 (3H, m, H-8, H-7, CH3CONH), 5.23 (1H, ddd, J = 11.8 Hz, J = 10.2 Hz, J = 4.5 Hz, H-4), 4.41 (1H, dd, J = 10.8 Hz, J = 2.2 Hz, H-6), 4.25 (1H, dd, J = 12.4 Hz, J = 2.6 Hz, H-9a), 4.15 (1H, q, J = 10.3 Hz, H-5), 4.08 (1H, dd, J = 12.5 Hz, J = 5.…”

“…13 Yield: 71% (30 mg; 0.048 mmol). 1 H NMR (400 MHz, CDCl3) δ 8.62 (1H, dt, J = 4.9 Hz, J = 1.3 Hz, H-Py), 8.50 (1H, s, CH-triazole), 8.13 (1H, dd, J = 7.9 Hz, J = 1.2 Hz, H-Py), 7.77 (1H, td, J = 7.7 Hz, J = 1.8 Hz, H-Py), 7.25-7.20 (1H, m, H-Py), 5.50 (1H, ddd, J = 8.4 Hz, J = 5.3 Hz, J = 2.9 Hz, H-8), 5.45 (1H, d, J = 9.8 Hz, CH3CONH), 5.39 (1H, dd, J = 8.6 Hz, J = 2.2 Hz, H-7), 5.23 (1H, ddd, J = 11.8 Hz, J = 10.2 Hz, J = 4.5 Hz, H-4), 4.38 (1H, ddd, J = 10.8 Hz, J = 2.2 Hz, H-6), 4.25 (1H, dd, J = 12.5 Hz, J = 2.9 Hz, H-9a), 4.18-4.08 (2H, m, H-5, H9-b), 3.79 (3H, s, CO2CH3), 3.48 (1H, dd, J = 13.3 Hz, J = 4.5 Hz, H-3eq), 2.71 (1H, dd, J = 13.3 Hz, J = 11.9 Hz, H-3ax), 2.17 (3H, s, CH3CO), 2.10 (3H, s, CH3CO), 2.07 (3H, s, CH3CO), 2.06 (3H, s, CH3CO), 1.91 (3H, s, CH3CONH). 13 Hz, H-3eq), 2.68 (1H, dd, J = 13.3 Hz, J = 12.0 Hz, H-3ax), 2.25 (3H, s, NCH3), 2.17 (3H, s, CH3CO), 2.11 (3H, s, CH3CO), 2.07 (3H, s, CH3CO), 2.04 (3H, s, CH3CO), 1.91 (3H, s, CH3CONH).…”

“…Amongst the diversity of glycans present in living organisms, N-acetylneuraminic acid (Neu5Ac, sialic acid) is typically found as a terminal unit of surface glycoconjugates and is crucial to various cellular recognition events in both physiological and pathological processes [1]. This distinctive negatively charged monosaccharide is the natural substrate for sialidases, which belong to different glycoside hydrolase (GH) families and play fundamental roles in the biology of humans, viruses, bacteria and parasitic protozoa by cleaving glycosidic linkages and releasing (or transferring) sialic acid from sialylated substrates [2].…”