Journal of Medicinal Chemistry pubs.acs.org/jmc Article Author Contributions Functions as a Nitrate Transporter in the Plasma Membrane. Proc. F.A., I.M.-T., B.G., and C.A. designed the research. L.D., N.P., Natl. Acad. Sci. U. S. A. 2012, 109, 13434−13439. A.C., I.F., C.D., P.-A.G., R.F., I.M.-T., and C.A. conducted the (9) Miyaji, T.; Echigo, N.; Hiasa, M.; Senoh, S.; Omote, H.; experiments. All authors analyzed the data. F.A., I.M.-T., B.G., Moriyama, Y. Identification of a Vesicular Aspartate Transporter. Proc. and C.A. wrote the paper. Natl. Acad. Sci. U. S. A. 2008, 105, 11720−11724. Funding (10) Lodder-Gadaczek, J.; Gieselmann, V.; Eckhardt, M. Vesicular Uptake of N-Acetylaspartylglutamate Is Catalysed by Sialin This work was supported by the Agence Nationale de la −38. (SLC17A5). Biochem. J. 2013, 454,31 Recherche (grant no. ANR-15-CE14-0001-02 to B.G.), the (11) Bardor, M.; Nguyen, D. H.; Diaz, S.; Varki, A. Mechanism of Association Nationale de la Recherche et de la Technologie Uptake and Incorporation of the Non-Human Sialic Acid N- ̀ (ANRT) and Dassault Systemes BIOVIA (CIFRE PhD Glycolylneuraminic Acid into Human Cells. J. Biol. Chem. 2005, ̀ 280, 4228−4237. scholarship no. 2018/0027 to A.C.), the Ministere de ́ (12) Chou, H.-H.; Takematsu, H.; Diaz, S.; Iber, J.; Nickerson, E.; l’Enseignement Superieur, de la Recherche et de l’Innovation ̂ ́ Wright, K. L.; Muchmore, E. A.; Nelson, D. L.; Warren, S. T.; Varki, (PhD fellowship to P.-A.G.), the Neuropole Region Ile-de- France (PhD fellowship to L.D.), and the Science Ambassador A. A Mutation in Human CMP-Sialic Acid Hydroxylase Occurred ̀ after the Homo-Pan Divergence. Proc. Natl. Acad. Sci. U. S. A. 1998, Program from Dassault Systemes BIOVIA (to A.C. and F.A.). 95, 11751−11756. Notes (13) Dhar, C.; Sasmal, A.; Varki, A. From “Serum Sickness” to The authors declare no competing financial interest. “Xenosialitis”: Past, Present, and Future Significance of the Non- ACKNOWLEDGMENTS Human Sialic Acid Neu5Gc. Front. Immunol. 2019, 10, 807. ■ (14) Kawanishi, K.; Dhar, C.; Do, R.; Varki, N.; Gordts, P. L. S. M.; ̈ ̈ Varki, A. Human Species-Specific Loss of CMP-N-Acetylneuraminic WethankDr.AijaKyttala from the Finnish Institute for Health Acid Hydroxylase Enhances Atherosclerosis via Intrinsic and Extrinsic and Welfare (THL) for acquiring the ethical permissions in Mechanisms. Proc. Natl. Acad. Sci. U. S. A. 2019, 116, 16036−16045. Finland and providing Salla fibroblasts for this study. C.B. ̈ thanks the glycoconjugate analysis facility PAGes (http:// (15) Bull, C.; Heise, T.; Adema, G. J.; Boltje, T. J. Sialic Acid plateforme-pages.univ-lille1.fr) and the FRABio research Mimetics to Target the Sialic Acid-Siglec Axis. Trends Biochem. Sci. federation. 2016, 41, 519−531. ̈ (16) Moons, S. J.; Adema, G. J.; Derks, M. T.; Boltje, T. J.; Bull, C. ABBREVIATIONS Sialic Acid Glycoengineering Using N-Acetylmannosamine and Sialic ■ Acid Analogs. Glycobiology 2019, 29, 433−445. Bz, benzoyl; Bzl, benzyl; Cbz, benzyloxycarbonyl; t-Bu, tert- (17) Aula, P.; Gahl, W. A. Disorders of Free Sialic Acid Storage. In butyl; Boc, tert-butoxycarbonyl; CDI, 1,1′-carbonyldimidazole; The Metabolic Molecular Basis of Inherited Disease; Eighth Edition; DIEA, diethylamine; DMF, dimethylformamide; Fmoc, fluo- Scriver, C. R., Beaudet, A. L., Sly, W. S., Valle, D., Childs, B., Kinzler, ren-9-ylmethoxycarbonyl; HBTU, 2-(1H-benzotriazol-1-yl)- K. W., Vogelstein, B., Eds.; McGraw-Hill: New-York, 2001, pp 5109− 1,1,3,3-tetramethyluronium hexafluorophosphate; MOMCl, 5120. ̈ methoxymethyl chloride; RT, room temperature; TFA, (18) Aula, N.; Salomaki, P.; Timonen, R.; Verheijen, F.; Mancini, G.; ̊ trifluoroacetic acid; THF, tetrahydrofuran; TMSCl, trimethyl- Mansson, J.-E.; Aula, P.; Peltonen, L. 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