Artificial and Natural Sialic Acid Precursors Influence the Angiogenic Capacity of Human Umbilical Vein Endothelial Cells

Molecules

Nils B. Bayer³  Uwe Schubert³  Zehra Sentürk³  Silvia Rudloff¹  Sandra Frank³  Heike Hausmann²  Hildegard Geyer³  Rudolf Geyer³  Klaus T. Preissner³ 

[1] Institute of Nutritional Science, Justus-Liebig-University, Wilhelmstr. 20, 35392 Giessen, Germany; E-Mail:;Institute of Organic Chemistry, Justus-Liebig University, Heinrich-Buff-Ring 58, 35392 Giessen, Germany; E-Mail:;Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, Friedrichstr. 24, 35392 Giessen, Germany; E-Mails:

关键词: glycoengineering;    artificial sialic acids;    mannosamine;    angiogenesis;   

DOI  :  10.3390/molecules18032571

来源: mdpi

【 摘 要 】

N-acetylneuraminic acid (Neu5Ac) represents the most common terminal carbohydrate residue in many mammalian glycoconjugates and is directly involved in a number of different physiological as well as pathological cellular processes. Endogenous sialic acids derive from the biosynthetic precursor molecule N-acetyl-D-mannosamine (ManNAc). Interestingly, N-acyl-analogues of D-mannosamine (ManN) can also be incorporated and converted into corresponding artificial sialic acids by eukaryotic cells. Within this study, we optimized a protocol for the chemical synthesis of various peracetylated ManN derivatives resulting in yields of approximately 100%. Correct molecular structures of the obtained products ManNAc, N-propanoyl-ManN (ManNProp) and N-butyl-ManN (ManNBut) were verified by GC-, ESI-MS- and NMR-analyses. By applying these substances to human umbilical vein endothelial cells (HUVECs), we could show that each derivative was metabolized to the corresponding N-acylneuraminic acid variant and subsequently incorporated into nascent glycoproteins. To investigate whether natural and/or artificial sialic acid precursors are able to modulate the angiogenic capacity of HUVECs, a spheroid assay was performed. By this means, an increase in total capillary length has been observed when cells incorporated N-butylneuraminic acid (Neu5But) into their glycoconjugates. In contrast, the natural precursor ManNAc inhibited the growth of capillaries. Thus, sialic acid precursors may represent useful agents to modulate blood vessel formation.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.