Synthesis of novel hapten derivatives of 1alpha,25-dihydroxy-vitamin D3 and its 20-epi analogue.
Hapten derivatives of 1alpha,25-dihydroxyvitamin D(3) and its 20-epimer were synthesized and conjugated to a carrier protein for raising polyclonal antibodies. The haptens were linked through spacers at C-16, thereby exposing both the A-ring and the side chain of the molecules, to maximize antibody specificity. The spacers were introduced via stereoselective hydroboration of 16-ene intermediates as the key step. In immunoassays, the antibodies raised toward the natural hormone were selective to this compound over derivatives with modifications in the A-ring or the side chain. The antibodies toward the 20-epimer, however, were unable to recognize modifications in the side chain.
Blaehr
Lars K A
LK
Medicinal Chemistry Research, LEO Pharma, DK-2750 Ballerup, Denmark. lars.blaehr@leo-pharma.com
Björkling
Fredrik
F
Calverley
Martin J
MJ
Binderup
Ernst
E
Begtrup
Mikael
M
D000906:Antibodies / Q000737:chemistry* / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000276:immunology; D020650:Combinatorial Chemistry Techniques; D006241:Haptens / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000906:Antibodies; D006241:Haptens; D002117:Calcitriol