Vitamin B12 Phosphate Conjugation and Its Effect on Binding to the Human B12 -Binding Proteins Intrinsic Factor and Haptocorrin.
The binding of vitamin B12 derivatives to human B12 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.
Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Keith
K
Ó Proinsias
Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Michał
M
Ociepa
Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Katarzyna
K
Pluta
Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Mikołaj
M
Chromiński
Department of Clinical Biochemistry, Aarhus University Hospital, Norrebrogade 44, 8000, Aarhus, Denmark.
Ebba
E
Nexo
Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224, Warsaw, Poland. dorot.gryko@icho.edu.pl.
Dorota
0000-0002-5197-4222
D
Gryko
D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D061565:Cycloaddition Reaction; D006801:Humans; D007437:Intrinsic Factor / Q000737:chemistry / Q000378:metabolism*; D008027:Light; D010710:Phosphates / Q000378:metabolism; D010782:Photolysis / Q000528:radiation effects; D011485:Protein Binding; D014155:Transcobalamins / Q000737:chemistry / Q000378:metabolism*; D014466:Ultraviolet Rays; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism
D000480:Alkynes; D001386:Azides; D010710:Phosphates; D014155:Transcobalamins; D003300:Copper; D007437:Intrinsic Factor; D014805:Vitamin B 12
click chemistry; glycoproteins; phosphates; substituent effects; vitamins