Vitamin B-12 Phosphate Conjugation and Its Effect on Binding to the Human B-12-Binding Proteins Intrinsic Factor and Haptocorrin

作者：Proinsias Keith O; Ociepa Michal; Pluta Katarzyna; Chrominski Mikolaj; Nexo Ebba; Gryko Dorota^*

来源：Chemistry - A European Journal, 2016, 22(24): 8282-8289.

DOI：10.1002/chem.201504898

• click chemistry
• glycoproteins
• phosphates
• substituent effects
• vitamins

The binding of vitamin B-12 derivatives to human B-12 transporter proteins is strongly influenced by the type and site of modification of the cobalamin original structure. We have prepared the first cobalamin derivative modified at the phosphate moiety. The reaction conditions were fully optimized and its limitations examined. The resulting derivatives, particularly those bearing terminal alkyne and azide groups, were isolated and used in copper-catalyzed alkyne-azide cycloaddition reactions (CuAAC). Their sensitivity towards light revealed their potential as photocleavable molecules. The binding abilities of selected derivatives were examined and compared with cyanocobalamin. The interaction of the alkylated derivatives with haptocorrin was less affected than the interaction with intrinsic factor. Furthermore, the configuration of the phosphate moiety was irrelevant to the binding process.

• 出版日期2016-6-6