title: Artificial and natural sialic acid precursors influence the angiogenic capacity of human umbilical vein endothelial cells.
abstract: 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.
authors: Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, Friedrichstr. 24, 35392 Giessen, Germany. nils.bayer@yahoo.de
authors: Nils B
authors: NB
authors: Bayer
authors: Uwe
authors: U
authors: Schubert
authors: Zehra
authors: Z
authors: Sentürk
authors: Silvia
authors: S
authors: Rudloff
authors: Sandra
authors: S
authors: Frank
authors: Heike
authors: H
authors: Hausmann
authors: Hildegard
authors: H
authors: Geyer
authors: Rudolf
authors: R
authors: Geyer
authors: Klaus T
authors: KT
authors: Preissner
authors: Sebastian P
authors: SP
authors: Galuska
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000737:chemistry / Q000494:pharmacology*; D053898:Biosynthetic Pathways; D002851:Chromatography, High Pressure Liquid; D006001:Glycoconjugates / Q000737:chemistry; D006023:Glycoproteins / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D013058:Mass Spectrometry; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*
chemical_list: D043925:Angiogenesis Inducing Agents; D006001:Glycoconjugates; D006023:Glycoproteins; D019158:N-Acetylneuraminic Acid