1. Design and synthesis of 4′-O-alkyl-chitobiosyl-4-methylumbelliferone as human chitinase fluorogenic substrates.
- Author
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Duivenvoorden, Boudewijn A., Ghauharali, Karen, Scheij, Saskia, Boot, Rolf G., Aerts, Johannes M.F.G., van der Marel, Gijsbert A., Overkleeft, Herman S., and Codée, Jeroen D.C.
- Subjects
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GAUCHER'S disease diagnosis , *CHITINASE , *GLYCOSYLATION , *MICHAELIS-Menten mechanism , *HEXOSAMINIDASE , *BIOCHEMICAL substrates , *BIOMARKERS , *SUBSTITUENTS (Chemistry) - Abstract
The synthesis of three fluorogenic chitobiosyl derivatives, modified at the non-reducing 4′-OH with, either a methyl, an isopropyl or a cyclohexylmethyl substituent, is described. The 4′-capped 4-methylumbelliferyl chitobiosides are hydrolysed by the human chitinase CHIT1 following Michaelis–Menten kinetics and in contrast to unmodified chitobiosyl-4-methylumbelliferone do not undergo transglycosylation. The compounds are also relatively poor hexosaminidase substrates and thus provide useful alternatives to 4′-deoxychitobiosyl-4-methylumbelliferone, previously reported by us as fluorogenic substrate to monitor CHIT1 activity as a marker for Gaucher disease state. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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