Synthesis of a molecular mimic of the Glc1Man9 oligoside as potential inhibitor of calnexin binding to DeltaF508 CFTR protein.
Deletion of phenylalanine at position 508 of the CFTR protein is associated with a severe form of cystic fibrosis. Biosynthetic arrest of the misfolded DeltaF508 CFTR protein in the endoplasmic reticulum is due to prolonged interaction with protein chaperones. In order to overcome this retention and thereby restore the delivery of the protein to the plasma membrane, a molecular mimic of the glycoprotein oligoside moiety has been designed and synthesized. Ability of this mimic to inhibit the binding of the natural Glc1Man9GlcNAc oligoside to calnexin has been measured.
Cherif
Slim
S
UMR 176 CNRS-Institut Curie, Section de Recherche, 26 rue d'Ulm, 75248 Cedex 05, Paris, France.
Leach
Michael R
MR
Williams
David B
DB
Monneret
Claude
C
D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D037281:Calnexin; D002240:Carbohydrate Sequence; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D018716:Molecular Mimicry; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D002135:Calcium-Binding Proteins; D009844:Oligosaccharides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D037281:Calnexin