Dienophile-Modified Mannosamine Derivatives for Metabolic Labeling of Sialic Acids: A Comparative Study.
Sialic acids play an important role in numerous cell adhesion processes, and sialylation levels are known to be altered under certain pathogenic conditions, such as cancer. Metabolic glycoengineering with mannosamine derivatives is a convenient way to introduce non-natural chemical reporter groups into sialylated glycoconjugates, offering the opportunity to label sialic acids by using bioorthogonal ligation chemistry. The labeling intensity depends not only on the rate of the ligation reaction but also on the extent to which the natural sialic acids are replaced by the modified ones; that is, the incorporation efficiency. Here, we present a comparative study of eight mannosamine derivatives featuring terminal alkenes as chemical reporter groups that can be labeled by an inverse-electron-demand Diels-Alder (DAinv) reaction. The derivatives differed in chain length as well as the type of linkage (carbamates, amides, and a urea) that connects the terminal alkene to the sugar. As a general trend, increasing chain lengths resulted in higher DAinv reactivity and, at the same time, reduced incorporation efficiency. Carbamates were better accepted than amides with the same chain length; nevertheless, the latter resulted in more intense cell-surface staining, visible by live-cell fluorescence microscopy. A urea derivative was also shown to be accepted.
University of Konstanz, Department of Chemistry and, Konstanz Research School Chemical Biology, KoRS-CB), 78457, Konstanz, Germany.
Jeremias E G A
JEGA
Dold
University of Konstanz, Department of Chemistry and, Konstanz Research School Chemical Biology, KoRS-CB), 78457, Konstanz, Germany.
Jessica
J
Pfotzer
University of Konstanz, Department of Chemistry and, Konstanz Research School Chemical Biology, KoRS-CB), 78457, Konstanz, Germany.
Anne-Katrin
AK
Späte
University of Konstanz, Department of Chemistry and, Konstanz Research School Chemical Biology, KoRS-CB), 78457, Konstanz, Germany.
Valentin
0000-0003-4043-6813
V
Wittmann
D000475:Alkenes / Q000737:chemistry; D000577:Amides / Q000737:chemistry; D002219:Carbamates / Q000737:chemistry; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D061565:Cycloaddition Reaction; D006001:Glycoconjugates / Q000737:chemistry* / Q000378:metabolism; D057809:HEK293 Cells; D006595:Hexosamines / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D012794:Sialic Acids / Q000737:chemistry* / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods*; D014508:Urea / Q000737:chemistry
D000475:Alkenes; D000577:Amides; D002219:Carbamates; D006001:Glycoconjugates; D006595:Hexosamines; D012794:Sialic Acids; C008322:mannosamine; D014508:Urea
Diels-Alder reaction; carbohydrates; mannosamines; metabolic engineering; sialic acids