Synthesis of labeled glycosyl phosphatidyl inositol (GPI) anchors

Article abstract of DOI:10.1002/(sici)1099-0690(199910)1999:10<2563::aid-ejoc2563>3.0.co;2-i

The exploration of the molecular and structural basis for the sorting of GPI-anchored proteins is based on labeled partial structures of GPI's which can be incorporated into the GPI anchor biosynthesis and cellular transport systems. To this end, from mannosyl donor 6 and the D-glucosaminyl-(1→6)D- myo-inositol derivative 7 as acceptor, the pseudotrisaccharide 8 was prepared. Compound 8 was transformed into the GPI partial structures 5a,b which contain the pseudotrisaccharide ligated to two different phosphatidyl residues. Compounds 5a,b have Boc protection at the 2- amino group of the glucosamine residue (2b-position) and a free amino group at the 6b-position. The 6b-amino group was used for the ligation of the 3-(7-nitrobenzofurazan-4- yl)aminopropanoyl group as a fluorescent label, the 5-azido-2-nitrobenzoyl and 4-azidophenylaminothiocarbonyl groups as photolabels, and the 4-azido-2- hydroxybenzoyl group as a radiolabel after the introduction of radioactive iodine by an electrophilic aromatic substitution. Thus, after acid-catalyzed removal of the protective groups, the unprotected target molecules 1-4 were obtained.