Synthesis, biologic activity, and protein binding characteristics of a new vitamin D analog, 22-hydroxyvitamin D3

Harpal S. Gill, James M. Londowski, Robert Corradino, Rajiv Kumar

Research output: Contribution to journalArticle

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Abstract

We synthesized a novel vitamin D analog, 22-hydroxyvitamin D3 9 and tested its biologic activity (and antivitamin properties) in vivo in vitamin D-deficient rats, and in vitro in the chick embryonic duodenum. We examined its ability to bind to the sterol carrier protein, vitamin D binding protein and the chick intestinal cytosol receptor for 1,25-dihydroxyvitamin D3. The new vitamin 9 was synthesized from 3β-hydroxy-22,23-dinorcholenic acid 1 in 12 steps. The vitamin 9 displayed no vitamin D agonist activity in the intestine or in bone in vivo and did not block the activity of vitamin D3 or 25-hydroxyvitamin D3. It was a weak vitamin D3 agonist in the chick embryonal duodenum in vitro. It did not antagonize the activity of 1,25-dihydroxyvitamin D3. Vitamin 9 bound to the chick intestinal cytosol receptor with low affinity. 22-Hydroxyvitamin D3 and various vitamin D sterols were bound to vitamin D binding protein in the following order: 25-hydroxyvitamin D3, (24R)-24,25-dihydroxyvitamin D3, and (25S)-25,26-dihydroxyvitamin D3 >22-hydroxyvitamin D3 >11α -hydroxyvitamin D3 >1,25-dihydroxy-vitamin D3 >vitamin D3. We conclude that the introduction of a hydroxyl group at C-22 in the side chain of the vitamin D3 molecule decreases its biological activity.

Original languageEnglish (US)
Pages (from-to)147-153
Number of pages7
JournalJournal of Steroid Biochemistry
Volume28
Issue number2
DOIs
StatePublished - 1987

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Cholecalciferol
Protein Binding
Vitamin D
Vitamins
Vitamin D-Binding Protein
Calcifediol
Duodenum
Cytosol
24,25-Dihydroxyvitamin D 3
Calcitriol Receptors
Calcitriol
Sterols
Bioactivity
Hydroxyl Radical
Intestines
Rats
Bone
Bone and Bones
Molecules
Acids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Synthesis, biologic activity, and protein binding characteristics of a new vitamin D analog, 22-hydroxyvitamin D3 . / Gill, Harpal S.; Londowski, James M.; Corradino, Robert; Kumar, Rajiv.

In: Journal of Steroid Biochemistry, Vol. 28, No. 2, 1987, p. 147-153.

Research output: Contribution to journalArticle

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