title: Design and synthesis of 4'-O-alkyl-chitobiosyl-4-methylumbelliferone as human chitinase fluorogenic substrates.
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.
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA Leiden, The Netherlands.
authors.forename: Boudewijn A
authors.initials: BA
authors.lastname: Duivenvoorden
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Karen
authors.initials: K
authors.lastname: Ghauharali
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Scheij
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Rolf G
authors.initials: RG
authors.lastname: Boot
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Johannes M F G
authors.initials: JM
authors.lastname: Aerts
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA Leiden, The Netherlands.
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA Leiden, The Netherlands. Electronic address: h.s.overkleeft@chem.leidenuniv.nl.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA Leiden, The Netherlands. Electronic address: jcodee@chem.leidenuniv.nl.
authors.forename: Jeroen D C
authors.initials: JD
authors.lastname: Codée
mesh_terms: D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D006596:Hexosaminidases / Q000378:metabolism*; D006801:Humans; D006923:Hymecromone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D013379:Substrate Specificity
chemical_list: D004187:Disaccharides; D006923:Hymecromone; D006596:Hexosaminidases; C086400:chitotriosidase
keywords: Chitotriosidase; Diagnostic tools; Fluorogenic substrates; Glycosylation; Marker enzyme