Synthesis of vitamin D3 analogues with A-ring modifications to directly measure vitamin D levels in biological samples.
C-3-substituted 25-hydroxyvitamin D3 analogues were synthesized as tools to directly measure levels of vitamin D in biological samples. The strategy involves vinyloxycarbonylation of the 3β-hydroxy group and formation of a carbamate bond with a hydroxyl or amino group at the end of the alkyl chain. Biotinylated conjugates of synthesized derivatives were generated to be linked with vitamin D binding protein (DBP). The spacer group present in the alkyl chain is important in the binding of antibodies to the analogue-DBP complex. When compared to 25-hydroxyvitamin D3-DBP, the binding of some antibodies to the analogue-DBP complex of the 25-hydroxyvitamin D3 derivative 10 that posses an 8-aminoctyl alkyl chain is significantly reduced, but this analogue displaced [26,27-(3)H]-25-hydroxyvitamin D3 from DBP. In contrast, the 8-hydroxyoctyl alkyl chain analogue 9 showed less displacement.
Departamento de Química Orgánica e Inorgánica and Instituto Universitario de Biotecnología de Asturias, Universidad de Oviedo, 33006 Oviedo, Asturias, Spain.
Alba
A
Hernández-Martín
Tania
T
González-García
Margaret
M
Lawlor
Lesley
L
Preston
Vicente
V
Gotor
Susana
S
Fernández
Miguel
M
Ferrero
D002112:Calcifediol / Q000031:analogs & derivatives / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D008968:Molecular Conformation; D014807:Vitamin D / Q000097:blood*
D014807:Vitamin D; D002112:Calcifediol
A-ring analogues; Biotin derivatives; Radiolabeled [26,27-(3)H]25-OH-D(3); Vitamin D; Vitamin D binding protein (DBP)