Prostaglandin photoaffinity probes: synthesis and binding affinity of C-18 substituted PGF2 alpha prostanoids bearing a perfluorinated aryl azide.
C-18 Phenoxy analogs of prostaglandin F2 alpha (PGF2 alpha) that possessed a perfluorinated aryl azide and an aryl iodide substituent were synthesized and evaluated as potential photoaffinity probes for PGF2 alpha. Prior studies indicated that only hydrophobic modifications in the omega-side chain of PGF2 alpha were compatible with high binding affinity, and this finding excluded the use of a hydroxyl-substituted C-18 phenoxy group as an activated aryl ring capable of radioiodination. Consequently, an alternate means of introducing the iodine substituent using an ipsosubstitution of a trimethylsilyl arene was developed. Although this strategy was successful from a synthetic perspective, the potential PGF2 alpha photoaffinity probe, (15S)-18-[3'-((4''-azido-2'',3'',5'',6''-tetrafluorophenyl)- methoxy) methyl-5'-iodophenoxy]-19,20-bisnorprostaglandin F2 alpha, exhibited only marginal competitive binding with [3H]-PGF2 alpha to ovine luteal cells and to plasma membranes of bovine corpora lutea. The hydrophobic but bulky C-18 substituent was presumably incompatible with effective receptor binding.
Golinski
M
M
Department of Chemistry, University of Kentucky, Lexington 40506.
Heine
M
M
Orlicky
D J
DJ
Fitz
T A
TA
Watt
D S
DS
D000345:Affinity Labels / Q000138:chemical synthesis* / Q000378:metabolism; D000527:Alprostadil / Q000378:metabolism; D001386:Azides / Q000737:chemistry*; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D005461:Fluorine / Q000737:chemistry*; D015394:Molecular Structure; D010777:Photochemistry
D000345:Affinity Labels; D001386:Azides; D005461:Fluorine; D015237:Dinoprost; D000527:Alprostadil