title: Synthesis of non-hydrolysable mimics of glycosylphosphatidylinositol (GPI) anchors.
abstract: Synthesis of first generation non-hydrolysable C-phosphonate GPI analogs, viz., 6-O-(2-amino-2-deoxy-α-d-glucopyranosyl)-d-myo-inositol-1-O-(sn-3,4-bis(palmitoyloxy)butyl-1-phosphonate) and 6-O-(2-amino-2-deoxy-α-d-glucopyranosyl)-d-myo-inositol-1-O-(sn-2,3-bis(palmitoyloxy)propyl-1-phosphonate) 23b, is reported. The target compounds were synthesized by the coupling of α-pseudodisaccharide 21 with phosphonic acids 18a and 18b respectively in quantitative yield followed by de-protection. These synthetic C-phosphonate GPI-probes were resistant to phosphatidylinositol specific phospholipase C (PI-PLC) and also showed moderate inhibition of the enzyme activity.
authors.affiliation: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180 001, India. ram@iiim.res.in ppsingh@iiim.ac.in.
authors.forename: Mahipal
authors.initials: M
authors.lastname: Yadav
authors.forename: Riya
authors.initials: R
authors.lastname: Raghupathy
authors.forename: Varma
authors.initials: V
authors.lastname: Saikam
authors.forename: Saidulu
authors.initials: S
authors.lastname: Dara
authors.forename: Parvinder Pal
authors.initials: PP
authors.lastname: Singh
authors.forename: Sanghapal D
authors.initials: SD
authors.lastname: Sawant
authors.forename: Satyajit
authors.initials: S
authors.lastname: Mayor
authors.forename: Ram A
authors.initials: RA
authors.lastname: Vishwakarma
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017261:Glycosylphosphatidylinositols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D017261:Glycosylphosphatidylinositols; D010738:Type C Phospholipases