Preparation of 17 alpha-iodoethynylandrosta- and 17 alpha-(2-iodoethenyl)androsta-4,6-dien-17 beta-ol-3-ones as active site-directed photoaffinity ligands for androgen-binding proteins.
Unsaturated analogues of androst-4-en-17 beta-ol-3-one, each with a 17 alpha-iodoethynyl or 17 alpha-(2-iodoethenyl) substituent, were prepared, and their relative binding affinities (RBAs) for androgen-binding protein (ABP) were compared with those of 5 alpha-androstan-17 beta-ol-3-one, androst-4-en-17 beta-ol-3-one, androsta-4,6-dien-17 beta-ol-3-one, and androsta-1,4,6-trien-17 beta-ol-3-one. These binding studies indicate that the iodine[125I] analogues of 17 alpha-iodoethynyl and 17 alpha-[(E)-2-iodoethenyl] derivatives of androsta-4,6-dien-17 beta-ol-3-one and androsta-1,4,6-trien-17 beta-ol-3-one will have RBAs at least twice as great as that of 5 alpha-androstan-17 beta-ol-3-one. They can be prepared from 17 alpha-ethynylandrosta-4-en-17 beta-ol-3-one, the final synthetic step using N-[125I]iodosuccinimide, and are potential radioiodinated, active site-directed photoaffinity ligands for ABP and testosterone-binding globulin.
Cruz
P J
PJ
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235.
Mason
N S
NS
Danzo
B J
BJ
Smith
H E
HE
D000345:Affinity Labels / Q000138:chemical synthesis*; D000727:Androgen-Binding Protein / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D015394:Molecular Structure; D010777:Photochemistry; D051381:Rats
D000345:Affinity Labels; D000727:Androgen-Binding Protein; D007457:Iodine Radioisotopes; D013196:Dihydrotestosterone; C078297:17-(2-iodoethynyl)androsta-4,6-dien-17-ol-3-one; C078296:17-(2-iodoethenyl)androsta-4,6-dien-17-ol-3-one