title: Efficient synthesis of isotopically pure isotope-coded affinity tagging reagents.
abstract: Synthesis of an isotopically pure d8-ICAT linker, N-[(5,5,6,6,8,8,9,9-2H)-13-biotinamido-4,7,10-trioxatridecanyl] tert-butyloxy carbamide (12), has been achieved in seven steps with an overall yield of 33%. Conjugation of exchange-inert d4-starting materials by classic etherification reaction yielded a pure synthon, carrying eight deuteriums that remained exchange-inert throughout subsequent reactions. This modified synthesis constitutes a significant improvement to the reported syntheses of "heavy" ICAT reagent in terms of expense, yield, and isotopic retention. This synthesis is easily adapted to incorporate additional deuterium atoms and is equally applicable for incorporation of either 13C and/or 18O. In addition, this synthesis allows for the introduction of different orthogonal functionalities and provides for a high yielding series of differentially encoded ICAT tags.
authors.affiliation: Department of Chemistry, 2036 Main Mall, University of British Columbia, Vancouver, B. C. V6T 1Z1 Canada, and PENCE Inc. (Protein Engineering Network of Centers of Excellence), 750 Heritage Medical Research Center, Edmonton, Alberta T6G-2S2 Canada.
authors.forename: Anupama
authors.initials: A
authors.lastname: Patel
authors.forename: David M
authors.initials: DM
authors.lastname: Perrin
mesh_terms: D000345:Affinity Labels / Q000138:chemical synthesis*; D001710:Biotin / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D002219:Carbamates / Q000138:chemical synthesis*; D002855:Chromatography, Thin Layer; D003903:Deuterium; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011868:Radioisotopes; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000345:Affinity Labels; D002219:Carbamates; D007202:Indicators and Reagents; C482340:N-(13-biotinamido-4,7,10-trioxatridecanyl) tert-butyloxy carbamide; D011868:Radioisotopes; D001710:Biotin; D003903:Deuterium