Protein-binding properties of 22-oxa-1.ALPHA.,25-dihydroxyvitamin D3, a synthetic analogue of 1.ALPHA.,25-dyhydroxyvitamin D3.

Abstract

Protein binding properties of 22-oxa-1.alpha.,25-dihydroxyvitamin D3 (22-oxa-1,25-D3), a synthetic analogue of 1.alpha.,25-dihydroxyvitamin D3 (1,25-D3), were compared with those of vitamin D3 derivatives. The order of binding affinity to the chick embryonic intestinal receptor was 1,25-D3>22-oxa-1,25-D3>25-hydroxyvitamin D3 (25-D3)>24R, 25-dihydroxyvitamin D3 (24,25-D3)>vitamin D3 (D3), while that to the rat plasma vitamin D-binding protein (DBP) was 25-D3>24,25D3>D3>1,25-D3>22-oxa-1,25-D3. The binding potencies of 22-oxa-1,25-D3 to the receptor and DBP were about 1/8 and 1/600 of the respective values of 1,25-D3. When the distribution of the tritiated compounds in human plasma components was examined by an in vitro polyacrylamide gel electrophoretic method, [3H]-22-oxa-1,25-D3 was found to bind only to the lipoproteins including chyromicron. These results suggest that the replacement of a carbon atom into an oxygen atom in the side chain structure of 1,25-D3 results significant decrease in the binding affinity to DBP and that 22-oxa-1,25-D3 is transported as a complex-form not with DBP but with lipoprotein to the target tissues.